Element contents
Series: Elements in Molecular Oncology
Targeting Oncogenic Driver Mutations in Lung Cancer
Published online by Cambridge University Press: 12 January 2023
Summary
The recent advances in the field of molecular diagnostic techniques have led to the identification of targetable alterations prompting a paradigm shift in the management of non-small cell lung cancer (NSCLC) and an era of precision oncology. This Element highlights the most clinically relevant oncogenic drivers other than EGFR, their management and current advancements in treatment. It also examines the different challenges in resistance to targeted therapies and diagnostic dilemmas for each oncogenic driver and the future direction of NSCLC management.
Keywords
- Type
- Element
- Information
- Series: Elements in Molecular OncologyOnline ISBN: 9781009336123Publisher: Cambridge University PressPrint publication: 02 February 2023
References
Howlader, N, Noone, AM, Krapcho, M et al. (eds.). SEER Cancer Statistics Review, 1975–2017. National Cancer Institute, Bethesda, MD, https://seercancer.gov/csr/1975_2017/, based on November 2019 SEER data submission, posted to the SEER website, April 2020.Google Scholar
Siegel, RL, Miller, KD, Fuchs, HE et al. Cancer statistics, 2022. CA Cancer J Clin 2022; 72 (1): 7–33.Google Scholar
Howlader, N, Forjaz, G, Mooradian, MJ et al. The effect of advances in lung-cancer treatment on population mortality. N Engl J Med 2020; 383 (7): 640–649.Google Scholar
Palmer, RH, Vernersson, E, Grabbe, C et al. Anaplastic lymphoma kinase: Signalling in development and disease. Biochem J 2009; 420 (3): 345–361.Google Scholar
Stoica, GE, Kuo, A, Aigner, A et al. Identification of anaplastic lymphoma kinase as a receptor for the growth factor pleiotrophin. J Biol Chem 2001; 276 (20): 16772–16779.CrossRefGoogle ScholarPubMed
Morris, SW, Kirstein, MN, Valentine, MB et al. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin’s lymphoma. Science 1994; 263 (5151): 1281–1284.Google Scholar
Murga-Zamalloa, C, Lim, MS. ALK-driven tumors and targeted therapy: Focus on crizotinib. Pharmgenomics Pers Med 2014; 7: 87–94.Google Scholar
Kadomatsu, K, Muramatsu, T. Midkine and pleiotrophin in neural development and cancer. Cancer Lett 2004; 204 (2): 127–143.CrossRefGoogle ScholarPubMed
Iwahara, T, Fujimoto, J, Wen, D et al. Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system. Oncogene 1997; 14 (4): 439–449.Google Scholar
Mossé, YP, Wood, A, Maris, JM. Inhibition of ALK signaling for cancer therapy. Clin Cancer Res 2009; 15 (18): 5609–5614.Google Scholar
Rodig, SJ, Mino-Kenudson, M, Dacic, S et al. Unique clinicopathologic features characterize ALK-rearranged lung adenocarcinoma in the western population. Clin Cancer Res 2009; 15 (16): 5216–5223.Google Scholar
Lou, N-N, Zhang, X-C, Chen, H-J et al. Clinical outcomes of advanced non-small-cell lung cancer patients with EGFR mutation, ALK rearrangement and EGFR/ALK co-alterations. Oncotarget 2016; 7 (40): 65185–65195.Google Scholar
Sasaki, T, Koivunen, J, Ogino, A et al. A novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors. Cancer Res 2011; 71 (18): 6051–6060.Google Scholar
Soda, M, Choi, YL, Enomoto, M et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007; 448 (7153): 561–566.CrossRefGoogle ScholarPubMed
Rikova, K, Guo, A, Zeng, Q et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 2007; 131 (6): 1190–1203.CrossRefGoogle ScholarPubMed
Gristina, V, La Mantia, M, Iacono, F et al. The emerging therapeutic landscape of ALK inhibitors in non-small cell lung cancer. Pharmaceuticals (Basel) 2020; 13 (12): E474.Google Scholar
Hallberg, B, Palmer, RH. Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology. Nat Rev Cancer 2013; 13 (10): 685–700.Google Scholar
Takeuchi, K, Choi, YL, Soda, M et al. Multiplex reverse transcription-PCR screening for EML4-ALK fusion transcripts. Clin Cancer Res 2008; 14 (20): 6618–6624.Google Scholar
Camidge, DR, Dziadziuszko, R, Peters, S et al. Updated efficacy and safety data and impact of the EML4-ALK fusion variant on the efficacy of alectinib in untreated ALK-positive advanced non-small cell lung cancer in the Global Phase III ALEX Study. J Thorac Oncol 2019; 14 (7): 1233–1243.Google Scholar
Christensen, JG, Zou, HY, Arango, ME et al. Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic lymphoma kinase and c-Met, in experimental models of anaplastic large-cell lymphoma. Mol Cancer Ther 2007; 6 (12 pt. 1): 3314–3322.Google Scholar
Kwak, EL, Bang, Y-J, Camidge, DR et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 2010; 363 (18): 1693–1703.CrossRefGoogle ScholarPubMed
Blackhall, F, Ross Camidge, D, Shaw, AT et al. Final results of the large-scale multinational trial PROFILE 1005: Efficacy and safety of crizotinib in previously treated patients with advanced/metastatic ALK-positive non-small-cell lung cancer. ESMO Open 2017; 2 (3): e000219.Google Scholar
Shaw, AT, Kim, D-W, Nakagawa, K et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 2013; 368 (25): 2385–2394.Google Scholar
Solomon, BJ, Mok, T, Kim D-W et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med 2014; 371 (23): 2167–2177.Google Scholar
Kim, D-W, Mehra, R, Tan, DSW et al. Activity and safety of ceritinib in patients with ALK-rearranged non-small-cell lung cancer (ASCEND-1): Updated results from the multicentre, open-label, phase 1 trial. Lancet Oncol 2016; 17 (4): 452–463.Google Scholar
Crinò, L, Ahn, M-J, De Marinis, F et al. Multicenter phase II study of whole-body and intracranial activity with ceritinib in patients with ALK-rearranged non-small-cell lung cancer previously treated with chemotherapy and crizotinib: Results from ASCEND-2. J Clin Oncol 2016; 34 (24): 2866–2873.Google Scholar
Soria, J-C, Tan, DSW, Chiari, R et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): A randomised, open-label, phase 3 study. Lancet 2017; 389 (10072): 917–929.Google Scholar
Shaw, AT, Kim, TM, Crinò, L et al. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): A randomised, controlled, open-label, phase 3 trial. Lancet Oncol 2017; 18 (7): 874–886.Google Scholar
Seto, T, Kiura, K, Nishio, M et al. CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): A single-arm, open-label, phase 1–2 study. Lancet Oncol 2013; 14 (7): 590–598.Google Scholar
Shaw, AT, Gandhi, L, Gadgeel, S et al. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: A single-group, multicentre, phase 2 trial. Lancet Oncol 2016; 17 (2): 234–242.CrossRefGoogle ScholarPubMed
Nakagawa, K, Hida, T, Nokihara, H et al. Final progression-free survival results from the J-ALEX study of alectinib versus crizotinib in ALK-positive non-small-cell lung cancer. Lung Cancer 2020; 139: 195–199.CrossRefGoogle ScholarPubMed
Yoshioka, H, Hida, T, Nokihara, H et al. Final OS analysis from the phase III J-ALEX study of alectinib (ALC) versus crizotinib (CRZ) in Japanese ALK-inhibitor naïve ALK-positive non-small cell lung cancer (ALK+ NSCLC). J Clin Oncol 2021; 39 (15 suppl.): 9022.Google Scholar
Peters, S, Camidge, DR, Shaw, AT et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med 2017; 377 (9): 829–838.Google Scholar
Mok, T, Camidge, DR, Gadgeel, SM et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol 2020; 31 (8): 1056–1064.Google Scholar
Gadgeel, S, Peters, S, Mok, T et al. Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study. Ann Oncol 2018; 29 (11): 2214–2222.CrossRefGoogle ScholarPubMed
Kim, DW, Tiseo, M, Ahn, MJ et al. Brigatinib in patients with crizotinib-refractory anaplastic lymphoma kinase-positive non-small-cell lung cancer: A randomized, multicenter phase II trial. J Clin Oncol 2017; 35 (22): 2490–2498.CrossRefGoogle ScholarPubMed
Huber, RM, Hansen, KH, Paz-Ares Rodríguez, L et al. Brigatinib in crizotinib-refractory ALK+ NSCLC: 2-year follow-up on systemic and intracranial outcomes in the phase 2 ALTA trial. J Thorac Oncol 2020; 15 (3): 404–415.Google Scholar
Camidge, DR, Kim, HR, Ahn, M-J et al. Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer. N Engl J Med 2018; 379 (21): 2027–2039.Google Scholar
Camidge, DR, Kim, HR, Ahn, M-J et al. Brigatinib versus crizotinib in advanced ALK inhibitor-naive ALK-positive non-small cell lung cancer: Second interim analysis of the phase III ALTA-1L trial. J Clin Oncol 2020; 38 (31): 3592–3603.Google Scholar
Solomon, BJ, Besse, B, Bauer, TM et al. Lorlatinib in patients with ALK-positive non-small-cell lung cancer: Results from a global phase 2 study. Lancet Oncol 2018; 19 (12): 1654–1667.Google Scholar
Shaw, AT, Bauer, TM, de Marinis, F et al. First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer.N Engl J Med 2020; 383 (21): 2018–2029.CrossRefGoogle ScholarPubMed
Gainor, JF, Shaw, AT. Emerging paradigms in the development of resistance to tyrosine kinase inhibitors in lung cancer. J Clin Oncol 2013; 31 (31): 3987–3996.Google Scholar
Gainor, JF, Dardaei, L, Yoda, S et al. Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer. Cancer Discov 2016; 6 (10): 1118–1133.CrossRefGoogle ScholarPubMed
Lin, JJ, Zhu, VW, Yoda, S et al. Impact of EML4-ALK variant on resistance mechanisms and clinical outcomes in ALK-positive lung cancer. J Clin Oncol 2018; 36 (12): 1199–1206.Google Scholar
Lucena-Araujo, AR, Moran, JP, VanderLaan, PA et al. De novo ALK kinase domain mutations are uncommon in kinase inhibitor-naïve ALK rearranged lung cancers. Lung Cancer 2016; 99: 17–22.Google Scholar
Shaw, AT, Felip, E, Bauer, TM et al. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: An international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol 2017; 18 (12): 1590–1599.Google Scholar
Shaw, AT, Solomon, BJ, Besse, B et al. ALK resistance mutations and efficacy of lorlatinib in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer. J Clin Oncol 2019; 37 (16): 1370–1379.Google Scholar
Smolle, E, Taucher, V, Lindenmann, J et al. Current knowledge about mechanisms of drug resistance against ALK inhibitors in non-small cell lung cancer. Cancers (Basel) 2021; 13 (4): 699.Google Scholar
Tyner, JW, Fletcher, LB, Wang, EQ et al. MET receptor sequence variants R970C and T992I lack transforming capacity. Cancer Res 2010; 70 (15): 6233–6237.Google Scholar
Guarino, M, Rubino, B, Ballabio, G. The role of epithelial-mesenchymal transition in cancer pathology. Pathology 2007; 39 (3): 305–318.Google Scholar
Fukuda, K, Takeuchi, S, Arai, S et al. Epithelial-to-mesenchymal transition is a mechanism of ALK inhibitor resistance in lung cancer independent of ALK mutation status. Cancer Res 2019; 79 (7): 1658–1670.Google Scholar
Cha, YJ, Cho, BC, Kim, HR et al. A case of ALK-rearranged adenocarcinoma with small cell carcinoma-like transformation and resistance to crizotinib. J Thorac Oncol 2016; 11 (5): e55–e58.Google Scholar
D’Incecco, A, Andreozzi, M, Ludovini, V et al. PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients. Br J Cancer 2015; 112 (1): 95–102.Google Scholar
Hong, S, Chen, N, Fang, W et al. Upregulation of PD-L1 by EML4-ALK fusion protein mediates the immune escape in ALK positive NSCLC: Implication for optional anti-PD-1/PD-L1 immune therapy for ALK-TKIs sensitive and resistant NSCLC patients. Oncoimmunology 2016; 5 (3): e1094598.Google Scholar
Gainor, JF, Shaw, AT, Sequist, LV et al. EGFR mutations and ALK rearrangements are associated with low response rates to PD-1 pathway blockade in non-small cell lung cancer: A retrospective analysis. Clin Cancer Res 2016; 22 (18): 4585–4593.CrossRefGoogle ScholarPubMed
Spigel, DR, Reynolds, C, Waterhouse, D et al. Phase 1/2 study of the safety and tolerability of nivolumab plus crizotinib for the first-line treatment of anaplastic lymphoma kinase translocation-positive advanced non-small cell lung cancer (CheckMate 370). J Thorac Oncol 2018; 13 (5): 682–688.Google Scholar
Sakamoto, H, Tsukaguchi, T, Hiroshima, S et al. CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant. Cancer Cell 2011; 19 (5): 679–690.CrossRefGoogle ScholarPubMed
Solomon, BJ, Ahn, JS, Barlesi, F et al. ALINA: A phase III study of alectinib versus chemotherapy as adjuvant therapy in patients with stage IB–IIIA anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC). J Clin Oncol 2019; 37 (15 suppl.): TPS8569.CrossRefGoogle Scholar
Horn, L, Wang, Z, Wu, G et al. Ensartinib vs crizotinib for patients with anaplastic lymphoma kinase-positive non-small cell lung cancer: A randomized clinical trial. JAMA Oncol 2021; 7 (11): 1617–1625.Google Scholar
Yang, J-J, Zhou, J, Yang, N et al. SAF-189s in previously treated patients with advanced ALK-rearranged non-small cell lung cancer (NSCLC): Results from the dose-finding portion in a single-arm, first-in-human phase I/II study. J Clin Oncol 2020; 38 (15 suppl.): e21689.Google Scholar
Fang, Y, Pan, H, Lu, S et al. A phase I study to evaluate safety, tolerability, pharmacokinetics, and preliminary antitumor activity of TQ-B3101. J Clin Oncol 2020; 38 (15 suppl.): e21705.CrossRefGoogle Scholar
Murray, BW, Zhai, D, Deng, W et al. TPX-0131, a potent CNS-penetrant, next-generation inhibitor of wild-type ALK and ALK-resistant mutations. Mol Cancer Ther 2021; 20 (9): 1499–1507.Google Scholar
Pelish, HE, Tangpeerachaikul, A, Kohl, NE et al. Abstract 1468: NUV-655 (NVL-655) is a selective, brain-penetrant ALK inhibitor with antitumor activity against the lorlatinib-resistant G1202R/L1196M compound mutation. Cancer Res 2021; 81 (13 suppl.): 1468.Google Scholar
Uguen, A, de Braekeleer, M. ROS1 fusions in cancer: A review. Future Oncol 2016; 12 (16): 1911–1928.Google Scholar
Acquaviva, J, Wong, R, Charest, A. The multifaceted roles of the receptor tyrosine kinase ROS in development and cancer. Biochim Biophys Acta 2009; 1795 (1): 37–52.Google ScholarPubMed
Birchmeier, C, Sharma, S, Wigler, M. Expression and rearrangement of the ROS1 gene in human glioblastoma cells. Proc Natl Acad Sci USA 1987; 84 (24): 9270–9274.Google Scholar
Gu, T-L, Deng, X, Huang, F et al. Survey of tyrosine kinase signaling reveals ROS kinase fusions in human cholangiocarcinoma. PLoS One 2011; 6 (1): e15640.Google Scholar
Lee, J, Lee, SE, Kang, SY et al. Identification of ROS1 rearrangement in gastric adenocarcinoma. Cancer 2013; 119 (9): 1627–1635.Google Scholar
Birch, AH, Arcand, SL, Oros, KK et al. Chromosome 3 anomalies investigated by genome wide SNP analysis of benign, low malignant potential and low grade ovarian serous tumours. PLoS One 2011; 6 (12): e28250.CrossRefGoogle ScholarPubMed
Gainor, JF, Shaw, AT. Novel targets in non-small cell lung cancer: ROS1 and RET fusions. Oncologist 2013; 18 (7): 865–875.CrossRefGoogle ScholarPubMed
Shaw, AT, Riely, GJ, Bang, YJ et al. Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): Updated results, including overall survival, from PROFILE 1001. Ann Oncol 2019; 30 (7): 1121–1126.Google Scholar
Wu, Y-L, Yang, JC-H, Kim, D-W et al. Phase II study of crizotinib in East Asian patients with ROS1-Positive advanced non-small-cell lung cancer. J Clin Oncol 2018; 36 (14): 1405–1411.Google Scholar
Michels, S, Massutí, B, Schildhaus, H-U et al. Safety and efficacy of crizotinib in patients with advanced or metastatic ROS1-rearranged lung cancer (EUCROSS): A European phase II clinical trial. J Thorac Oncol 2019; 14 (7): 1266–1276.Google Scholar
Roys, A, Chang, X, Liu, Y et al. Resistance mechanisms and potent-targeted therapies of ROS1-positive lung cancer. Cancer Chemother Pharmacol 2019; 84 (4): 679–688.Google Scholar
Lim, SM, Kim, HR, Lee, J-S et al. Open-label, multicenter, phase II study of ceritinib in patients with non-small-cell lung cancer harboring ROS1 rearrangement. J Clin Oncol 2017; 35 (23): 2613–2618.Google Scholar
Azelby, CM, Sakamoto, MR, Bowles, DW. ROS1 targeted therapies: Current status. Curr Oncol Rep 2021; 23 (8): 94.Google Scholar
Ardini, E, Menichincheri, M, Banfi, P et al. Entrectinib, a pan-TRK, ROS1, and ALK inhibitor with activity in multiple molecularly defined cancer indications. Mol Cancer Ther 2016; 15 (4): 628–639.CrossRefGoogle ScholarPubMed
Drilon, A, Siena, S, Dziadziuszko, R et al. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: Integrated analysis of three phase 1–2 trials. Lancet Oncol 2020; 21 (2): 261–270.Google Scholar
Barlesi, F, Drilon, A, Braud, FD et al. Entrectinib in locally advanced or metastatic ROS1 fusion-positive non-small cell lung cancer (NSCLC): Integrated analysis of ALKA-372–001, STARTRK-1 and STARTRK-2. Ann Oncol 2019; 30: ii48–ii49.CrossRefGoogle Scholar
Shaw, AT, Solomon, BJ, Chiari, R et al. Lorlatinib in advanced ROS1-positive non-small-cell lung cancer: A multicentre, open-label, single-arm, phase 1–2 trial. Lancet Oncol 2019; 20 (12): 1691–1701.Google Scholar
Lin, JJ, Choudhury, NJ, Yoda, S et al. Spectrum of mechanisms of resistance to crizotinib and lorlatinib in ROS1 fusion-positive lung cancer. Clin Cancer Res 2021; 27 (10): 2899–2909.Google Scholar
Drilon, A, Somwar, R, Wagner, JP et al. A novel crizotinib-resistant solvent-front mutation responsive to cabozantinib therapy in a patient with ROS1-rearranged lung cancer. Clin Cancer Res 2016; 22 (10): 2351–2358.Google Scholar
Drilon, A, Ou, S-HI, Cho, BC et al. Repotrectinib (TPX-0005) Is a next-generation ROS1/TRK/ALK inhibitor that potently inhibits ROS1/TRK/ALK solvent- front mutations. Cancer Discov 2018; 8 (10): 1227–1236.Google Scholar
Cho, BC, Doebele, RC, Lin, J et al. MA11.07 phase 1/2 TRIDENT-1 study of repotrectinib in patients with ROS1+ or NTRK+ advanced solid tumors. J Thorac Oncol 2021; 16 (3): S174–S175.Google Scholar
Ou, SI, Fujiwara, Y, Shaw, AT et al. Efficacy of taletrectinib (AB-106/DS-6051b) in ROS1+ NSCLC: An updated pooled analysis of U.S. and Japan phase 1 studies. JTO Clin Res Rep 2021; 2 (1): 100108.Google Scholar
Zhou, C, Fan, H, Wang, Y et al. Taletrectinib (AB-106; DS-6051b) in metastatic non-small cell lung cancer (NSCLC) patients with ROS1 fusion: Preliminary results of TRUST. J Clin Oncol 2021; 39 (15 suppl.): 9066.Google Scholar
Ai, X, Wang, Q, Cheng, Y et al. Safety but limited efficacy of ensartinib in ROS1-positive NSCLC: A single-arm, multicenter phase 2 study. J Thorac Oncol 2021; 16 (11): 1959–1963.CrossRefGoogle ScholarPubMed
Takahashi, M, Ritz, J, Cooper, GM. Activation of a novel human transforming gene, ret, by DNA rearrangement. Cell 1985; 42 (2): 581–588.Google Scholar
Ibanez, CF. Structure and physiology of the RET receptor tyrosine kinase. Cold Spring Harb Perspect Biol 2013; 5 (2).Google Scholar
Besset, V, Scott, RP, Ibanez, CF. Signaling complexes and protein-protein interactions involved in the activation of the Ras and phosphatidylinositol 3-kinase pathways by the c-Ret receptor tyrosine kinase. J Biol Chem 2000; 275 (50): 39159–39166.Google Scholar
Coulpier, M, Anders, J, Ibanez, CF. Coordinated activation of autophosphorylation sites in the RET receptor tyrosine kinase: Importance of tyrosine 1062 for GDNF mediated neuronal differentiation and survival. J Biol Chem 2002; 277 (3): 1991–1999.CrossRefGoogle ScholarPubMed
De Vita, G, Melillo, RM, Carlomagno, F et al. Tyrosine 1062 of RET-MEN2A mediates activation of Akt (protein kinase B) and mitogen-activated protein kinase pathways leading to PC12 cell survival. Cancer Res 2000; 60 (14): 3727–3731.Google Scholar
Jain, S, Encinas, M, Johnson, EM Jr. et al. Critical and distinct roles for key RET tyrosine docking sites in renal development. Genes Dev 2006; 20 (3): 321–333.Google Scholar
Jijiwa, M, Kawai, K, Fukihara, J et al. GDNF-mediated signaling via RET tyrosine 1062 is essential for maintenance of spermatogonial stem cells. Genes Cells 2008; 13 (4): 365–374.CrossRefGoogle ScholarPubMed
Romei, C, Ciampi, R, Elisei, R. A comprehensive overview of the role of the RET proto-oncogene in thyroid carcinoma. Nat Rev Endocrinol 2016; 12 (4): 192–202.CrossRefGoogle ScholarPubMed
Santoro, M, Moccia, M, Federico, G et al. RET gene fusions in malignancies of the thyroid and other tissues. Genes (Basel) 2020; 11 (4).Google Scholar
Larouche, V, Akirov, A, Thomas, CM et al. A primer on the genetics of medullary thyroid cancer. Curr Oncol 2019; 26 (6): 389–394.Google Scholar
Fagin, JA, Wells, SA Jr. Biologic and clinical perspectives on thyroid cancer. N Engl J Med 2016; 375 (11): 1054–1067.Google Scholar
Grubbs, EG, Ng, PK, Bui, J et al. RET fusion as a novel driver of medullary thyroid carcinoma. J Clin Endocrinol Metab 2015; 100 (3): 788–793.CrossRefGoogle ScholarPubMed
Kohno, T, Tabata, J, Nakaoku, T. REToma: A cancer subtype with a shared driver oncogene. Carcinogenesis 2020; 41 (2): 123–129.Google Scholar
Yakushina, VD, Lerner, LV, Lavrov, AV. Gene fusions in thyroid cancer. Thyroid 2018; 28 (2): 158–167.Google Scholar
Accardo, G, Conzo, G, Esposito, D et al. Genetics of medullary thyroid cancer: An overview. Int J Surg 2017; 41 (suppl. 1): S2–S6.Google Scholar
Li, AY, McCusker, MG, Russo, A et al. RET fusions in solid tumors. Cancer Treat Rev 2019; 81: 101911.Google Scholar
Drilon, A, Lin, JJ, Filleron, T et al. Frequency of brain metastases and multikinase inhibitor outcomes in patients with RET-rearranged lung cancers. J Thorac Oncol 2018; 13 (10): 1595–1601.Google Scholar
Gautschi, O, Milia, J, Filleron, T et al. Targeting RET in patients with RET-rearranged lung cancers: Results From the global, multicenter RET registry. J Clin Oncol 2017; 35 (13): 1403–1410.Google Scholar
Drilon, A, Hu, ZI, Lai, GGY et al. Targeting RET-driven cancers: Lessons from evolving preclinical and clinical landscapes. Nat Rev Clin Oncol 2018; 15 (3): 151–167.Google Scholar
Hess, LM, Han, Y, Zhu, YE et al. Characteristics and outcomes of patients with RET-fusion positive non-small lung cancer in real-world practice in the United States. BMC Cancer 2021; 21 (1): 28.Google Scholar
Drilon, A, Oxnard, GR, Tan, DSW et al. Efficacy of selpercatinib in RET fusion-positive non-small-cell lung cancer. N Engl J Med 2020; 383 (9): 813–824.Google Scholar
Kato, S, Subbiah, V, Marchlik, E et al. RET aberrations in diverse cancers: Next-generation sequencing of 4,871 patients. Clin Cancer Res 2017; 23 (8): 1988–1997.CrossRefGoogle Scholar
Morra, F, Luise, C, Visconti, R et al. New therapeutic perspectives in CCDC6 deficient lung cancer cells. Int J Cancer 2015; 136 (9): 2146–2157.Google Scholar
Bellelli, R, Castellone, MD, Guida, T et al. NCOA4 transcriptional coactivator inhibits activation of DNA replication origins. Mol Cell 2014; 55 (1): 123–137.CrossRefGoogle ScholarPubMed
Das, TK, Cagan, RL. KIF5B-RET oncoprotein signals through a multi-kinase signaling hub. Cell Rep 2017; 20 (10): 2368–2383.Google Scholar
Vaishnavi, A, Schubert, L, Rix, U et al. EGFR mediates responses to small-molecule drugs targeting oncogenic fusion kinases. Cancer Res 2017; 77 (13): 3551–3563.Google Scholar
Nakaoku, T, Kohno, T, Araki, M et al. A secondary RET mutation in the activation loop conferring resistance to vandetanib. Nat Commun 2018; 9 (1): 625.Google Scholar
Hida, T, Velcheti, V, Reckamp, KL et al. A phase 2 study of lenvatinib in patients with RET fusion-positive lung adenocarcinoma. Lung Cancer 2019; 138: 124–130.Google Scholar
Drilon, A, Rekhtman, N, Arcila, M et al. Cabozantinib in patients with advanced RET-rearranged non-small-cell lung cancer: An open-label, single-centre, phase 2, single-arm trial. Lancet Oncol 2016; 17 (12): 1653–1660.Google Scholar
Drilon, A, Wang, L, Hasanovic, A et al. Response to cabozantinib in patients with RET fusion-positive lung adenocarcinomas. Cancer Discov 2013; 3 (6): 630–635.CrossRefGoogle ScholarPubMed
Lee, SH, Lee, JK, Ahn, MJ et al. Vandetanib in pretreated patients with advanced non-small cell lung cancer-harboring RET rearrangement: A phase II clinical trial. Ann Oncol 2017; 28 (2): 292–297.Google Scholar
Hayman, SR, Leung, N, Grande, JP et al. VEGF inhibition, hypertension, and renal toxicity. Curr Oncol Rep 2012; 14 (4): 285–294.Google Scholar
Lacouture, ME, Anadkat, MJ, Bensadoun, RJ et al. Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities. Support Care Cancer 2011; 19 (8): 1079–1095.Google Scholar
Choudhury, NJ, Drilon, A. Decade in review: A new era for RET-rearranged lung cancers. Transl Lung Cancer Res 2020; 9 (6): 2571–2580.Google Scholar
Fancelli, S, Caliman, E, Mazzoni, F et al. Chasing the target: New phenomena of resistance to novel selective RET inhibitors in lung cancer. Updated evidence and future perspectives. Cancers (Basel) 2021; 13 (5).Google Scholar
Gainor, JF, Curigliano, G, Kim, D-W et al. Pralsetinib for RET fusion-positive non-small-cell lung cancer (ARROW): A multi-cohort, open-label, phase 1/2 study.Lancet Oncol 2021; 22 (7): 959–969.Google Scholar
Chang, H, Sung, JH, Moon, SU et al. EGF induced RET inhibitor resistance in CCDC6-RET lung cancer cells. Yonsei Med J 2017; 58 (1): 9–18.Google Scholar
Blakely, CM, Watkins, TBK, Wu, W et al. Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers. Nat Genet 2017; 49 (12): 1693–1704.Google Scholar
Suda, K, Mitsudomi, T. Emerging oncogenic fusions other than ALK, ROS1, RET, and NTRK in NSCLC and the role of fusions as resistance mechanisms to targeted therapy. Transl Lung Cancer Res 2020; 9 (6): 2618–2628.Google Scholar
Piotrowska, Z, Isozaki, H, Lennerz, JK et al. Landscape of acquired resistance to osimertinib in EGFR-mutant NSCLC and clinical validation of combined EGFR and RET inhibition with osimertinib and BLU-667 for acquired RET fusion. Cancer Discov 2018; 8 (12): 1529–1539.Google Scholar
Rich, TA, Reckamp, KL, Chae, YK et al. Analysis of cell-free DNA from 32,989 advanced cancers reveals novel co-occurring activating RET alterations and oncogenic signaling pathway aberrations. Clin Cancer Res 2019; 25 (19): 5832–5842.Google Scholar
Rotow, J, Patel, J, Hanley, M et al. FP14.07 combination osimertinib plus selpercatinib for EGFR-mutant non-small cell lung cancer (NSCLC) with acquired RET fusions. J Thorac Oncol 2021; 16 (3).Google Scholar
Turning Point Therapeutics. Turning Point Therapeutics Announces Initial Clinical Data from Phase 1/2 SWORD-1 Study of RET Inhibitor TPX-0046. Turning Point Therapeutics, San Diego, CA, April 7, 2021.Google Scholar
Schoffski, P, Cho, BC, Italiano, A et al. BOS172738, a highly potent and selective RET inhibitor, for the treatment of RET-altered tumors including RET-fusion+ NSCLC and RET-mutant MTC: Phase 1 study results. J Clin Oncol 2021; 39 (15 suppl.): 3008.Google Scholar
Moccia, M, Frett, B, Zhang, L et al. Bioisosteric discovery of NPA101.3, a second-generation RET/VEGFR2 inhibitor optimized for single-agent polypharmacology. J Med Chem 2020; 63 (9): 4506–4516.Google Scholar
Cooper, CS PM, Blair, DG, Tainsky, MA et al. Molecular cloning of a new transforming gene from a chemically transformed human cell line. Nature 1984; 311 (5981): 29–33.Google Scholar
Furge, KA, Zhang, YW, Vande Woude, GF. Met receptor tyrosine kinase: Enhanced signaling through adapter proteins. Oncogene 2000; 19 (49): 5582–5589.Google Scholar
Birchmeier, C, Birchmeier, W, Gherardi, E et al. Met, metastasis, motility and more. Nat Rev Mol Cell Biol 2003; 4 (12): 915–925.Google Scholar
Cecchi, F, Rabe, DC, Bottaro, DP. Targeting the HGF/Met signaling pathway in cancer therapy. Expert Opin Ther Targets 2012; 16 (6): 553–572.Google Scholar
Kolatsi-Joannou, M, Moore, R, Winyard, PJ et al. Expression of hepatocyte growth factor/scatter factor and its receptor, MET, suggests roles in human embryonic organogenesis. Pediatr Res 1997; 41 (5): 657–665.Google Scholar
Reungwetwattana, T, Liang, Y, Zhu, V et al. The race to target MET exon 14 skipping alterations in non-small cell lung cancer: The why, the how, the who, the unknown, and the inevitable. Lung Cancer 2017; 103: 27–37.Google Scholar
Lamberti, G, Andrini, E, Sisi, M et al. Beyond EGFR, ALK and ROS1: Current evidence and future perspectives on newly targetable oncogenic drivers in lung adenocarcinoma. Crit Rev Oncol Hematol 2020; 156: 103119.Google Scholar
Deheuninck, J, Goormachtigh, G, Foveau, B et al. Phosphorylation of the MET receptor on juxtamembrane tyrosine residue 1001 inhibits its caspase-dependent cleavage. Cell Signal 2009; 21 (9): 1455–1463.Google Scholar
Peschard, P, Fournier, TM, Lamorte, L et al. Mutation of the c-Cbl TKB domain binding site on the MET receptor tyrosine kinase converts it into a transforming protein. Molecular Cell 2001; 8 (5): 995–1004.Google Scholar
Cortot, AB, Kherrouche, Z, Descarpentries, C et al. Exon 14 deleted MET receptor as a new biomarker and target in cancers. J Natl Cancer Inst 2017; 109 (5).Google Scholar
Cheng, TL, Chang, MY, Huang, SY et al. Overexpression of circulating c-met messenger RNA is significantly correlated with nodal stage and early recurrence in non-small cell lung cancer. Chest 2005; 128 (3): 1453–1460.Google Scholar
Ma, PC, Jagadeeswaran, R, Jagadeesh, S et al. Functional expression and mutations of c-Met and its therapeutic inhibition with SU11274 and small interfering RNA in non-small cell lung cancer. Cancer Res 2005; 65 (4): 1479–1488.Google Scholar
Socinski, MA, Pennell, NA, Davies, KD. MET exon 14 skipping mutations in non-small-cell lung cancer: An overview of biology, clinical outcomes, and testing considerations. JCO Precis Oncol 2021; 5.Google Scholar
Schrock, AB, Frampton, GM, Suh, J et al. Characterization of 298 patients with lung cancer harboring MET exon 14 skipping alterations. J Thorac Oncol 2016; 11 (9): 1493–1502.Google Scholar
Liu, X, Jia, Y, Stoopler, MB et al. Next-generation sequencing of pulmonary sarcomatoid carcinoma reveals high frequency of actionable MET gene mutations. J Clin Oncol 2016; 34 (8): 794–802.Google Scholar
Awad, MM, Oxnard, GR, Jackman, DM et al. MET exon 14 mutations in non-small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-MET overexpression. J Clin Oncol 2016; 34 (7): 721–730.Google Scholar
Digumarthy, SR, Mendoza, DP, Zhang, EW et al. Clinicopathologic and imaging features of non-small-cell lung cancer with MET exon 14 skipping mutations. Cancers (Basel) 2019; 11 (12).Google Scholar
Lee, GD, Lee, SE, Oh, DY et al. MET exon 14 skipping mutations in lung adenocarcinoma: Clinicopathologic implications and prognostic values. J Thorac Oncol 2017; 12 (8): 1233–1246.Google Scholar
Tong, JH, Yeung, SF, Chan, AW et al. MET amplification and exon 14 splice site mutation define unique molecular subgroups of non-small cell lung carcinoma with poor prognosis. Clin Cancer Res 2016; 22 (12): 3048–3056.Google Scholar
Awad, MM, Leonardi, GC, Kravets, S et al. Impact of MET inhibitors on survival among patients with non-small cell lung cancer harboring MET exon 14 mutations: A retrospective analysis. Lung Cancer 2019; 133: 96–102.Google Scholar
Awad, MM, Lee, JK, Madison, R et al. Characterization of 1,387 NSCLCs with MET exon 14 (METex14) skipping alterations (SA) and potential acquired resistance (AR) mechanisms. J Clin Oncol 2020; 38 (15 suppl.): 9511.Google Scholar
Frampton, GM, Ali, SM, Rosenzweig, M et al. Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors. Cancer Discov 2015; 5 (8): 850–859.Google Scholar
Lee, JK, Madison, R, Classon, A et al. Characterization of non-small-cell lung cancers with MET exon 14 skipping alterations detected in tissue or liquid: Clinicogenomics and real-world treatment patterns. JCO Precis Oncol 2021; 5.Google Scholar
Drilon, A, Clark, JW, Weiss, J et al. Antitumor activity of crizotinib in lung cancers harboring a MET exon 14 alteration. Nat Med 2020; 26 (1): 47–51.Google Scholar
Landi, L, Chiari, R, Tiseo, M et al. Crizotinib in MET-deregulated or ROS1-rearranged pretreated non-small cell lung cancer (METROS): A phase II, prospective, multicenter, two-arms trial. Clin Cancer Res 2019; 25 (24): 7312–7319.Google Scholar
Wolf, J, Seto, T, Han, JY et al. Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer. N Engl J Med 2020; 383 (10): 944–957.Google Scholar
Paik, PK, Felip, E, Veillon, R et al. Tepotinib in non-small-cell lung cancer with MET exon 14 skipping mutations. N Engl J Med 2020; 383 (10): 931–943.Google Scholar
Lu, S, Fang, J, Li, X et al. Phase II study of savolitinib in patients (pts) with pulmonary sarcomatoid carcinoma (PSC) and other types of non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations (METex14+). J Clin Oncol 2020; 38 (15 suppl.): 9519.Google Scholar
Wang, SXY, Zhang, BM, Wakelee, HA et al. Case series of MET exon 14 skipping mutation-positive non-small-cell lung cancers with response to crizotinib and cabozantinib. Anticancer Drugs 2019; 30 (5): 537–541.Google Scholar
D’Arcangelo, M, Tassinari, D, De Marinis, F et al. P2.01–15 phase II single arm study of cabozantinib in non-small cell lung cancer patients with MET deregulation (CABinMET). J Thorac Oncol 2019; 14 (10).Google Scholar
Suzawa, K, Offin, M, Schoenfeld, AJ et al. Acquired MET exon 14 alteration drives secondary resistance to epidermal growth factor receptor tyrosine kinase inhibitor in EGFR-mutated lung cancer. JCO Precis Oncol 2019; 3.Google Scholar
Heist, RS, Sequist, LV, Borger, D et al. Acquired resistance to crizotinib in NSCLC with MET exon 14 skipping. J Thorac Oncol 2016; 11 (8): 1242–1245.Google Scholar
Recondo, G, Bahcall, M, Spurr, LF et al. Molecular mechanisms of acquired resistance to MET tyrosine kinase inhibitors in patients with MET exon 14-mutant NSCLC. Clin Cancer Res 2020; 26 (11): 2615–2625.Google Scholar
Bahcall, M, Sim, T, Paweletz, CP et al. Acquired METD1228V mutation and resistance to MET inhibition in lung cancer. Cancer Discov 2016; 6 (12): 1334–1341.Google Scholar
Fujino, T, Kobayashi, Y, Suda, K et al. Sensitivity and resistance of MET exon 14 mutations in lung cancer to eight MET tyrosine kinase inhibitors in vitro. J Thorac Oncol 2019; 14 (10): 1753–1765.Google Scholar
Engstrom, LD, Aranda, R, Lee, M et al. Glesatinib exhibits antitumor activity in lung cancer models and patients harboring MET exon 14 mutations and overcomes mutation-mediated resistance to type I MET inhibitors in nonclinical models. Clin Cancer Res 2017; 23 (21): 6661–6672.Google Scholar
Schoenfeld, AJ, Chan, JM, Kubota, D et al. Tumor analyses reveal squamous transformation and off-target alterations as early resistance mechanisms to first-line osimertinib in EGFR-mutant lung cancer. Clin Cancer Res 2020; 26 (11): 2654–2663.Google Scholar
Bahcall, M, Awad, MM, Sholl, LM et al. Amplification of wild-type KRAS imparts resistance to crizotinib in MET exon 14 mutant non-small cell lung cancer. Clin Cancer Res 2018; 24 (23): 5963–5976.Google Scholar
Ali, SM, Sanford, EM, Klempner, SJ et al. Prospective comprehensive genomic profiling of advanced gastric carcinoma cases reveals frequent clinically relevant genomic alterations and new routes for targeted therapies. Oncologist 2015; 20 (5): 499–507.Google Scholar
Bardelli, A, Corso, S, Bertotti, A et al. Amplification of the MET receptor drives resistance to anti-EGFR therapies in colorectal cancer. Cancer Discov 2013; 3 (6): 658–673.Google Scholar
Okuda, K, Sasaki, H, Yukiue, H et al. Met gene copy number predicts the prognosis for completely resected non-small cell lung cancer. Cancer Sci 2008; 99 (11): 2280–2285.Google Scholar
Kim, JH, Kim, HS, Kim, BJ. Prognostic value of MET copy number gain in non-small-cell lung cancer: An updated meta-analysis. J Cancer 2018; 9 (10): 1836–1845.Google Scholar
Noonan, SA, Berry, L, Lu, X et al. Identifying the appropriate FISH criteria for defining MET copy number-driven lung adenocarcinoma through oncogene overlap analysis. J Thorac Oncol 2016; 11 (8): 1293–1304.Google Scholar
Camidge, DR, Otterson, GA, Clark, JW et al. Crizotinib in patients (pts) with MET-amplified non-small cell lung cancer (NSCLC): Updated safety and efficacy findings from a phase 1 trial. J Clin Oncol 2018; 36 (15 suppl.): 9062.Google Scholar
Ko, B, He, T, Gadgeel, S et al. MET/HGF pathway activation as a paradigm of resistance to targeted therapies. Ann Transl Med 2017; 5 (1): 4.Google Scholar
Papadimitrakopoulou, VA, Wu, YL, Han, JY et al. Analysis of resistance mechanisms to osimertinib in patients with EGFR T790M advanced NSCLC from the AURA3 study. Ann Oncol 2018; 29 (52): 20932–20937.Google Scholar
Bean, J, Brennan, C, Shih, JY et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci USA 2007; 104 (52): 20932–20937.Google Scholar
Wu, YL, Zhang, L, Kim, DW et al. Phase Ib/II study of capmatinib (INC280) plus gefitinib after failure of epidermal growth factor receptor (EGFR) inhibitor therapy in patients with EGFR-mutated, MET factor-dysregulated non-small-cell lung cancer. J Clin Oncol 2018; 36 (31): 3101–3109.Google Scholar
Wu, Y-L, Cheng, Y, Zhou, J et al. Tepotinib plus gefitinib in patients with EGFR-mutant non-small-cell lung cancer with MET overexpression or MET amplification and acquired resistance to previous EGFR inhibitor (INSIGHT study): An open-label, phase 1b/2, multicentre, randomised trial. Lancet Resp Med 2020; 8 (11): 1132–1143.Google Scholar
Deng, W, Zhai, D, Rogers, E et al. Abstract 1325: TPX-0022, a polypharmacology inhibitor of MET/CSF1R/SRC inhibits tumor growth by promoting anti-tumor immune responses. Cancer Res 2019; 79 (13 suppl.): 1325.Google Scholar
Goel, VK, Deng, W, Zhai, D et al. Abstract 1444: TPX-0022, a potent MET/SRC/CSF1R inhibitor that modulates the tumor immune microenvironment in preclinical models. Cancer Res 2021; 81 (13 suppl.): 1444.Google Scholar
Hong, DS, Sen, S, Park, H et al. A phase I, open-label, multicenter, first-in-human study of the safety, tolerability, pharmacokinetics, and antitumor activity of TPX-0022, a novel MET/CSF1R/SRC inhibitor, in patients with advanced solid tumors harboring genetic alterations in MET. J Clin Oncol 2020; 38 (15 suppl.): TPS3663.Google Scholar
Strickler, JH, Weekes, CD, Nemunaitis, J et al. First-in-human phase I, dose-escalation and -expansion study of telisotuzumab vedotin, an antibody-drug conjugate targeting c-Met, in patients with advanced solid tumors. J Clin Oncol 2018; 36 (33): 3298–3306.Google Scholar
Strickler, JH, LoRusso, P, Yen, C-J et al. Phase 1, open-label, dose-escalation, and expansion study of ABT-700, an anti-C-met antibody, in patients (pts) with advanced solid tumors. J Clin Oncol 2014; 32 (15 suppl.): 2507.Google Scholar
Ocampo, C, Wu, J, Dey, J et al. P2.01–19 phase 2 study of telisotuzumab vedotin (Teliso-V) in previously treated c-MET+ non-small cell lung cancer: Trial in progress. J Thorac Oncol 2019; 14 (10).Google Scholar
Spira, A, Krebs, M, Cho, BC et al. OA15.03 amivantamab in non-small cell lung cancer (NSCLC) with MET exon 14 skipping (METex14) mutation: Initial results from CHRYSALIS. J Thorac Oncol 2021; 16 (10 suppl.): S874–S875.Google Scholar
Pantsar, T. The current understanding of KRAS protein structure and dynamics. Comput Struct Biotechnol J 2020; 18: 189–198.Google Scholar
Ahearn, IM, Haigis, K, Bar-Sagi, D et al. Regulating the regulator: Post-translational modification of RAS. Nat Rev Mol Cell Biol 2011; 13 (1): 39–51.Google Scholar
Bos, JL, Rehmann, H, Wittinghofer, A. GEFs and GAPs: Critical elements in the control of small G proteins. Cell 2007; 129 (5): 865–877.Google Scholar
Stephen, AG, Esposito, D, Bagni, RK et al. Dragging ras back in the ring. Cancer Cell 2014; 25 (3): 272–281.Google Scholar
Prior, IA, Hood, FE, Hartley, JL. The frequency of Ras mutations in cancer. Cancer Res 2020; 80 (14): 2969–2974.Google Scholar
Hunter, JC, Manandhar, A, Carrasco, MA et al. Biochemical and structural analysis of common cancer-associated KRAS mutations. Mol Cancer Res 2015; 13 (9): 1325–1335.Google Scholar
Molina-Arcas, M, Samani, A, Downward, J. Drugging the undruggable: Advances on RAS targeting in cancer. Genes 2021; 12 (6): 899.Google Scholar
Moore, AR, Rosenberg, SC, McCormick, F et al. RAS-targeted therapies: Is the undruggable drugged? Nat Rev Drug Discov 2020; 19 (8): 533–552.Google Scholar
Spencer-Smith, R, O’Bryan, JP. Direct inhibition of RAS: Quest for the Holy Grail? Semin Cancer Biol 2019; 54: 138–148.Google Scholar
Blumenschein, GR, Smit, EF, Planchard, D et al. A randomized phase II study of the MEK1/MEK2 inhibitor trametinib (GSK1120212) compared with docetaxel in KRAS-mutant advanced non-small-cell lung cancer (NSCLC)†. Ann Oncol 2015; 26 (5): 894–901.Google Scholar
Ostrem, JM, Peters, U, Sos, ML et al. K-RAS(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature 2013; 503 (7477): 548–551.Google Scholar
Lanman, BA, Allen, JR, Allen, JG et al. Discovery of a covalent inhibitor of KRASG12C (AMG 510) for the treatment of solid tumors. J Med Chem 2020; 63 (1): 52–65.Google Scholar
Canon, J, Rex, K, Saiki, AY et al. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature 2019; 575 (7781): 217–223.Google Scholar
Hong, DS, Fakih, MG, Strickler, JH et al. KRASG12C inhibition with sotorasib in advanced solid tumors. N Engl J Med 2020; 383 (13): 1207–1217.Google Scholar
Skoulidis, F, Li, BT, Govindan, R et al. Overall survival and exploratory subgroup analyses from the phase 2 CodeBreaK 100 trial evaluating sotorasib in pretreated KRAS p.G12C mutated non-small cell lung cancer. J Clin Oncol 2021; 39 (15 suppl.): 9003.Google Scholar
Skoulidis, F, Li, BT, Dy, GK et al. Sotorasib for lung cancers with KRAS p.G12C mutation. N Engl J Med 2021; 384 (25): 2371–2381.Google Scholar
Fell, JB, Fischer, JP, Baer, BR et al. Identification of the clinical development candidate MRTX849, a covalent KRASG12C inhibitor for the treatment of cancer. J Med Chem 2020; 63 (13): 6679–6693.Google Scholar
Ou, SI, Janne, PA, Leal, TA et al. First-in-human phase I/IB dose-finding study of adagrasib (MRTX849) in patients with advanced KRAS(G12C) solid tumors (KRYSTAL-1). J Clin Oncol 2022; 40 (23): JCO2102752.Google Scholar
Koga, T, Suda, K, Fujino, T et al. KRAS secondary mutations that confer acquired resistance to KRAS G12C inhibitors, sotorasib and adagrasib, and overcoming strategies: Insights from in vitro experiments. J Thorac Oncol 2021; 16 (8): 1321–1332.Google Scholar
Tanaka, N, Lin, JJ, Li, C et al. Clinical acquired resistance to KRASG12C inhibition through a novel KRAS switch-II pocket mutation and polyclonal alterations converging on RAS-MAPK reactivation. Cancer Discov 2021; 11 (8): 1913–1922.Google Scholar
Awad, MM, Liu, S, Rybkin, II et al. Acquired resistance to KRASG12C inhibition in cancer. N Engl J Med 2021; 384 (25): 2382–2393.Google Scholar
Jeanson, A, Tomasini, P, Souquet-Bressand, M et al. Efficacy of immune checkpoint inhibitors in KRAS-mutant non-small cell lung cancer (NSCLC). J Thorac Oncol 2019; 14 (6): 1095–1101.Google Scholar
Xie, M, Xu, X, Fan, Y. KRAS-mutant non-small cell lung cancer: An emerging promisingly treatable subgroup. Front Oncol 2021; 11: 672612.Google Scholar
Gadgeel, S, Rodriguez-Abreu, D, Felip, E et al. KRAS mutational status and efficacy in KEYNOTE-189: Pembrolizumab (pembro) plus chemotherapy (chemo) vs placebo plus chemo as first-line therapy for metastatic non-squamous NSCLC. Ann Oncol 2019; 30: xi64–xi65.Google Scholar
Peng, S-B, Si, C, Zhang, Y et al. Abstract 1259: Preclinical characterization of LY3537982, a novel, highly selective and potent KRAS-G12C inhibitor. Cancer Res 2021; 81 (13 suppl.): 1259.Google Scholar
Savarese, F, Gollner, A, Rudolph, D et al. Abstract 1271: In vitro and in vivo characterization of BI 1823911 – A novel KRASG12C selective small molecule inhibitor. Cancer Res 2021; 81 (13 suppl.): 1271.Google Scholar
Nichols, RJ, Cregg, J, Schulze, CJ et al. Abstract 1261: A next generation tri-complex KRASG12C(ON) inhibitor directly targets the active, GTP-bound state of mutant RAS and may overcome resistance to KRASG12C(OFF) inhibition. Cancer Res 2021; 81 (13 suppl.): 1261.Google Scholar
Mainardi, S, Mulero-Sánchez, A, Prahallad, A et al. SHP2 is required for growth of KRAS-mutant non-small-cell lung cancer in vivo. Nat Med 2018; 24 (7): 961–967.Google Scholar
Hallin, J, Engstrom, LD, Hargis, L et al. The KRASG12C inhibitor MRTX849 provides insight toward therapeutic susceptibility of KRAS-mutant cancers in mouse models and patients. Cancer Discov 2020; 10 (1): 54–71.Google Scholar
Yaeger, R, Corcoran, RB. Targeting alterations in the RAF-MEK pathway. Cancer Discov 2019; 9 (3): 329–341.Google Scholar
Imielinski, M, Berger, AH, Hammerman, PS et al. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 2012; 150 (6): 1107–1120.Google Scholar
Menzies, AM, Yeh, I, Botton, T et al. Clinical activity of the MEK inhibitor trametinib in metastatic melanoma containing BRAF kinase fusion. Pigment Cell Melanoma Res 2015; 28 (5): 607–610.Google Scholar
Roskoski, R Jr. RAF protein-serine/threonine kinases: Structure and regulation. Biochem Biophys Res Commun 2010; 399 (3): 313–317.Google Scholar
Pratilas, CA, Taylor, BS, Ye, Q et al. (V600E)BRAF is associated with disabled feedback inhibition of RAF-MEK signaling and elevated transcriptional output of the pathway. Proc Natl Acad Sci USA 2009; 106 (11): 4519–4524.Google Scholar
Weiss, RH, Maga, EA, Ramirez, A. MEK inhibition augments Raf activity, but has variable effects on mitogenesis, in vascular smooth muscle cells. Am J Physiol 1998; 274 (6): C1521–C1529.Google Scholar
Lake, D, Correa, SA, Muller, J. Negative feedback regulation of the ERK1/2 MAPK pathway. Cell Mol Life Sci 2016; 73 (23): 4397–4413.Google Scholar
Ho, CC, Liao, WY, Lin, CA et al. Acquired BRAF V600E mutation as resistant mechanism after treatment with osimertinib. J Thorac Oncol 2017; 12 (3): 567–572.Google Scholar
Lee, C, Rhee, I. Important roles of protein tyrosine phosphatase PTPN12 in tumor progression. Pharmacol Res 2019; 144: 73–78.Google Scholar
Smiech, M, Leszczynski, P, Kono, H et al. Emerging BRAF mutations in cancer progression and their possible effects on transcriptional networks. Genes (Basel) 2020; 11 (11).CrossRefGoogle ScholarPubMed
Wan, PTC, Garnett, MJ, Roe, SM et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 2004; 116 (6): 855–867.Google Scholar
Kobayashi, M, Sonobe, M, Takahashi, T et al. Clinical significance of BRAF gene mutations in patients with non-small cell lung cancer. Anticancer Res 2011; 31 (12): 4619–4623.Google Scholar
Davies, H, Bignell, GR, Cox, C et al. Mutations of the BRAF gene in human cancer. Nature 2002; 417 (6892): 949–954.Google Scholar
Brose, MS, Volpe, P, Feldman, M et al. BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res 2002; 62 (23): 6997–7000.Google Scholar
Bracht, JWP, Karachaliou, N, Bivona, T et al. BRAF mutations classes I, II, and III in NSCLC patients included in the SLLIP trial: The need for a new pre-clinical treatment rationale. Cancers (Basel) 2019; 11 (9).Google Scholar
Roviello, G, D’Angelo, A, Sirico, M et al. Advances in anti-BRAF therapies for lung cancer. Invest New Drugs 2021; 39 (3): 879–890.Google Scholar
Pratilas, CA, Hanrahan, AJ, Halilovic, E et al. Genetic predictors of MEK dependence in non-small cell lung cancer. Cancer Res 2008; 68 (22): 9375–9383.Google Scholar
Paik, PK, Arcila, ME, Fara, M et al. Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol 2011; 29 (15): 2046–2051.Google Scholar
Tan, I, Stinchcombe, TE, Ready, NE et al. Therapeutic outcomes in non-small cell lung cancer with BRAF mutations: A single institution, retrospective cohort study. Transl Lung Cancer Res 2019; 8 (3): 258–267.Google Scholar
Sheikine, Y, Pavlick, D, Klempner, SJ et al. BRAF in lung cancers: Analysis of patient cases reveals recurrent BRAF mutations, fusions, kinase duplications, and concurrent alterations. JCO Precis Oncol 2018; 2.Google Scholar
Vojnic, M, Kubota, D, Kurzatkowski, C et al. Acquired BRAF rearrangements induce secondary resistance to EGFR therapy in EGFR-mutated lung cancers. J Thorac Oncol 2019; 14 (5): 802–815.Google Scholar
Frisone, D, Friedlaender, A, Malapelle, U et al. A BRAF new world. Crit Rev Oncol Hematol 2020; 152: 103008.Google Scholar
Dagogo-Jack, I, Martinez, P, Yeap, BY et al. Impact of BRAF mutation class on disease characteristics and clinical outcomes in BRAF-mutant lung cancer. Clin Cancer Res 2019; 25 (1): 158–165.Google Scholar
Yousem, SA, Nikiforova, M, Nikiforov, Y. The histopathology of BRAF-V600E-mutated lung adenocarcinoma. Am J Surg Pathol 2008; 32 (9): 1317–1321.Google Scholar
Marchetti, A, Felicioni, L, Malatesta, S et al. Clinical features and outcome of patients with non-small-cell lung cancer harboring BRAF mutations. J Clin Oncol 2011; 29 (26): 3574–3579.Google Scholar
Cardarella, S, Ogino, A, Nishino, M et al. Clinical, pathologic, and biologic features associated with BRAF mutations in non-small cell lung cancer. Clin Cancer Res 2013; 19 (16): 4532–4540.Google Scholar
Planchard, D, Besse, B, Groen, HJM et al. Dabrafenib plus trametinib in patients with previously treated BRAFV600E-mutant metastatic non-small cell lung cancer: An open-label, multicentre phase 2 trial. Lancet Oncol 2016; 17 (7): 984–993.Google Scholar
Jones, JC, Renfro, LA, Al-Shamsi, HO et al. (Non-V600) BRAF mutations define a clinically distinct molecular subtype of metastatic colorectal cancer. J Clin Oncol 2017; 35 (23): 2624–2630.Google Scholar
Reddy, VP, Gay, LM, Elvin, JA et al. BRAF fusions in clinically advanced non-small cell lung cancer: An emerging target for anti-BRAF therapies. J Clin Oncol 2017; 35 (15 suppl.): 9072.Google Scholar
Zhao, J, Guo, R, Ai, X et al. BRAF fusion in lung cancer. J Clin Oncol 2020; 38 (15 suppl.): e21598.Google Scholar
Wang, CY, Hsia, JY, Li, CH et al. Lung adenocarcinoma With primary LIMD1-BRAF fusion treated with MEK inhibitor: A case report. Clin Lung Cancer 2021; 22 (6): e878–e880.Google Scholar
Robert, C, Karaszewska, B, Schachter, J et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med 2015; 372 (1): 30–39.Google Scholar
Grob, JJ, Amonkar, MM, Karaszewska, B et al. Comparison of dabrafenib and trametinib combination therapy with vemurafenib monotherapy on health-related quality of life in patients with unresectable or metastatic cutaneous BRAF Val600-mutation-positive melanoma (COMBI-v): Results of a phase 3, open-label, randomised trial. Lancet Oncol 2015; 16 (13): 1389–1398.Google Scholar
Poulikakos, PI, Zhang, C, Bollag, G et al. RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature 2010; 464 (7287): 427–430.Google Scholar
Sturm, OE, Orton, R, Grindlay, J et al. The mammalian MAPK/ERK pathway exhibits properties of a negative feedback amplifier. Sci Signal 2010; 3 (153): ra90.Google Scholar
Hatzivassiliou, G, Song, K, Yen, I et al. RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. Nature 2010; 464 (7287): 431–435.Google Scholar
Heidorn, SJ, Milagre, C, Whittaker, S et al. Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell 2010; 140 (2): 209–221.Google Scholar
Flaherty, KT, Puzanov, I, Kim, KB et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 2010; 363 (9): 809–819.Google Scholar
Su, F, Viros, A, Milagre, C et al. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med 2012; 366 (3): 207–215.Google Scholar
Planchard, D, Smit, EF, Groen, HJM et al. Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant metastatic non-small-cell lung cancer: An open-label, phase 2 trial. Lancet Oncol 2017; 18 (10): 1307–1316.Google Scholar
Planchard, D, Besse, B, Kim, TM et al. Updated survival of patients (pts) with previously treated BRAF V600E-mutant advanced non-small cell lung cancer (NSCLC) who received dabrafenib (D) or D + trametinib (T) in the phase II BRF113928 study. J Clin Oncol 2017; 35 (15 suppl.): 9075.Google Scholar
Planchard, D, Besse, B, Groen, HJM et al. Phase 2 study of dabrafenib plus trametinib in patients with BRAF V600E-mutant metastatic NSCLC: Updated 5-year survival rates and genomic analysis. J Thorac Oncol 2022; 17 (1): 103–115.Google Scholar
Odogwu, L, Mathieu, L, Blumenthal, G et al. FDA approval summary: Dabrafenib and trametinib for the treatment of metastatic non-small cell lung cancers harboring BRAF V600E mutations. Oncologist 2018; 23 (6): 740–745.Google Scholar
Larkin, J, Ascierto, PA, Dreno, B et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med 2014; 371 (20): 1867–1876.Google Scholar
Subbiah, V, Gervais, R, Riely, G et al. Efficacy of vemurafenib in patients with non-small-cell lung cancer with BRAF V600 mutation: An open-label, single-arm cohort of the histology-independent VE-BASKET study. JCO Precis Oncol 2019; 3.Google Scholar
Mazieres, J, Cropet, C, Montane, L et al. Vemurafenib in non-small-cell lung cancer patients with BRAF(V600) and BRAF(nonV600) mutations. Ann Oncol 2020; 31 (2): 289–294.Google Scholar
Gautschi, O, Milia, J, Cabarrou, B et al. Targeted therapy for patients with BRAF-mutant lung cancer: Results from the European EURAF cohort. J Thorac Oncol 2015; 10 (10): 1451–1457.Google Scholar
Nebhan, CA, Johnson, DB, Sullivan, RJ et al. Efficacy and safety of trametinib in non-V600 BRAF mutant melanoma: A phase II study. Oncologist 2021; 26 (9): 731–e1498.Google Scholar
Johnson, DB, Zhao, F, Noel, M et al. Trametinib activity in patients with solid tumors and lymphomas harboring BRAF non-V600 mutations or fusions: Results from NCI-MATCH (EAY131). Clin Cancer Res 2020; 26 (8): 1812–1819.Google Scholar
Dankner, M, Lajoie, M, Moldoveanu, D et al. Dual MAPK inhibition is an effective therapeutic strategy for a subset of class II BRAF mutant melanomas. Clin Cancer Res 2018; 24 (24): 6483–6494.Google Scholar
Noeparast, A, Teugels, E, Giron, P et al. Non-V600 BRAF mutations recurrently found in lung cancer predict sensitivity to the combination of trametinib and dabrafenib. Oncotarget 2017; 8 (36): 60094–60108.Google Scholar
Alvarez, JGB, Otterson, GA. Agents to treat BRAF-mutant lung cancer. Drugs Context 2019; 8: 212566.Google Scholar
Reyes, R, Mayo-de-Las-Casas, C, Teixido, C et al. Clinical benefit from BRAF/MEK inhibition in a double non-V600E BRAF mutant lung adenocarcinoma: A case report. Clin Lung Cancer 2019; 20 (3): e219–e223.Google Scholar
Turshudzhyan, A, Vredenburgh, J. A rare p.T599dup BRAF mutant NSCLC in a non-smoker. Curr Oncol 2020; 28 (1): 196–202.Google Scholar
Negrao, MV, Raymond, VM, Lanman, RB et al. Molecular landscape of BRAF-mutant NSCLC reveals an association between clonality and driver mutations and identifies targetable non-V600 driver mutations. J Thorac Oncol 2020; 15 (10): 1611–1623.Google Scholar
Dudnik, E, Peled, N, Nechushtan, H et al. BRAF mutant lung cancer: Programmed death ligand 1 expression, tumor mutational burden, microsatellite instability status, and response to immune check-point inhibitors. J Thorac Oncol 2018; 13 (8): 1128–1137.Google Scholar
Guisier, F, Dubos-Arvis, C, Vinas, F et al. Efficacy and safety of anti-PD-1 immunotherapy in patients with advanced NSCLC with BRAF, HER2, or MET mutations or RET translocation: GFPC 01–2018. J Thorac Oncol 2020; 15 (4): 628–636.Google Scholar
Mazieres, J, Drilon, AE, Mhanna, L et al. Efficacy of immune-checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC) patients harboring activating molecular alterations (ImmunoTarget). J Clin Oncol 2018; 36 (15 suppl.): 9010.Google Scholar
Sullivan, RJ, Hollebecque, A, Flaherty, KT et al. A phase I study of LY3009120, a pan-RAF inhibitor, in patients with advanced or metastatic cancer. Mol Cancer Ther 2020; 19 (2): 460–467.Google Scholar
Paraiso, KH, Xiang, Y, Rebecca, VW et al. PTEN loss confers BRAF inhibitor resistance to melanoma cells through the suppression of BIM expression. Cancer Res 2011; 71 (7): 2750–2760.Google Scholar
Manzano, JL, Layos, L, Buges, C et al. Resistant mechanisms to BRAF inhibitors in melanoma. Ann Transl Med 2016; 4 (12): 237.Google Scholar
Gibney, GT, Smalley, KS. An unholy alliance: Cooperation between BRAF and NF1 in melanoma development and BRAF inhibitor resistance. Cancer Discov 2013; 3 (3): 260–263.Google Scholar
Carlino, MS, Fung, C, Shahheydari, H et al. Preexisting MEK1P124 mutations diminish response to BRAF inhibitors in metastatic melanoma patients. Clin Cancer Res 2015; 21 (1): 98–105.Google Scholar
Nassar, KW, Hintzsche, JD, Bagby, SM et al. Targeting CDK4/6 represents a therapeutic vulnerability in acquired BRAF/MEK inhibitor-resistant melanoma. Mol Cancer Ther 2021; 20 (10): 2049–2060.Google Scholar
Yao, Z, Torres, NM, Tao, A et al. BRAF mutants evade ERK-dependent feedback by different mechanisms that determine their sensitivity to pharmacologic inhibition. Cancer Cell 2015; 28 (3): 370–383.Google Scholar
Corcoran, RB, Ebi, H, Turke, AB et al. EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib. Cancer Discov 2012; 2 (3): 227–235.Google Scholar
Prahallad, A, Sun, C, Huang, S et al. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature 2012; 483 (7387): 100–103.Google Scholar
Abravanel, DL, Nishino, M, Sholl, LM et al. An acquired NRAS Q61K mutation in BRAF V600E-mutant lung adenocarcinoma resistant to dabrafenib plus trametinib. J Thorac Oncol 2018; 13 (8): e131–e133.Google Scholar
Facchinetti, F, Lacroix, L, Mezquita, L et al. Molecular mechanisms of resistance to BRAF and MEK inhibitors in BRAF(V600E) non-small cell lung cancer. Eur J Cancer 2020; 132: 211–223.Google Scholar
Niemantsverdriet, M, Schuuring, E, Elst, AT et al. KRAS mutation as a resistance mechanism to BRAF/MEK inhibition in NSCLC. J Thorac Oncol 2018; 13 (12): e249–e251.Google Scholar
Rudin, CM, Hong, K, Streit, M. Molecular characterization of acquired resistance to the BRAF inhibitor dabrafenib in a patient with BRAF-mutant non-small-cell lung cancer. J Thorac Oncol 2013; 8 (5): e41–42.Google Scholar
Schrock, AB, Zhu, VW, Hsieh, WS et al. Receptor tyrosine kinase fusions and BRAF kinase fusions are rare but actionable resistance mechanisms to EGFR tyrosine kinase inhibitors. J Thorac Oncol 2018; 13 (9): 1312–1323.Google Scholar
Huang, Y, Gan, J, Guo, K et al. Acquired BRAF V600E mutation mediated resistance to osimertinib and responded to osimertinib, dabrafenib, and trametinib combination therapy. J Thorac Oncol 2019; 14 (10): e236–e237.Google Scholar
Meng, P, Koopman, B, Kok, K et al. Combined osimertinib, dabrafenib and trametinib treatment for advanced non-small-cell lung cancer patients with an osimertinib-induced BRAF V600E mutation. Lung Cancer 2020; 146: 358–361.Google Scholar
Solassol, J, Vendrell, JA, Senal, R et al. Challenging BRAF/EGFR co-inhibition in NSCLC using sequential liquid biopsies. Lung Cancer 2019; 133: 45–47.Google Scholar
Zhou, F, Zhao, W, Chen, X et al. Response to the combination of dabrafenib, trametinib and osimertinib in a patient with EGFR-mutant NSCLC harboring an acquired BRAF(V600E) mutation. Lung Cancer 2020; 139: 219–220.Google Scholar
Dagogo-Jack, I, Piotrowska, Z, Cobb, R et al. Response to the combination of osimertinib and trametinib in a patient with EGFR-mutant NSCLC harboring an acquired BRAF fusion. J Thorac Oncol 2019; 14 (10): e226–e228.Google Scholar
Ross, JS, Wang, K, Chmielecki, J et al. The distribution of BRAF gene fusions in solid tumors and response to targeted therapy. Int J Cancer 2016; 138 (4): 881–890.Google Scholar
Okimoto, RA, Lin, L, Olivas, V et al. Preclinical efficacy of a RAF inhibitor that evades paradoxical MAPK pathway activation in protein kinase BRAF-mutant lung cancer. Proc Natl Acad Sci USA 2016; 113 (47): 13456–13461.Google Scholar
Yao, Z, Gao, Y, Su, W et al. RAF inhibitor PLX8394 selectively disrupts BRAF dimers and RAS-independent BRAF-mutant-driven signaling. Nat Med 2019; 25 (2): 284–291.Google Scholar
Koumaki, K, Kontogianni, G, Kosmidou, V et al. BRAF paradox breakers PLX8394, PLX7904 are more effective against BRAFV600Epsilon CRC cells compared with the BRAF inhibitor PLX4720 and shown by detailed pathway analysis. Biochim Biophys Acta Mol Basis Dis 2021; 1867 (4): 166061.Google Scholar
Janku, F, Sherman, EJ, Parikh, AR et al. Interim results from a phase 1/2 precision medicine study of PLX8394: A next generation BRAF inhibitor. Eur J Cancer 2020; 138: S2–S3.Google Scholar
Kim, TW, Lee, J, Shin, SJ et al. Belvarafenib, a novel pan-RAF inhibitor, in solid tumor patients harboring BRAF, KRAS, or NRAS mutations: Phase I study. J Clin Oncol 2019; 37 (15 suppl.): 3000.Google Scholar
Varga, A, Soria, JC, Hollebecque, A et al. A first-in-human phase I study to evaluate the ERK1/2 inhibitor GDC-0994 in patients with advanced solid tumors. Clin Cancer Res 2020; 26 (6): 1229–1236.Google Scholar
Moschos, SJ, Sullivan, RJ, Hwu, WJ et al. Development of MK-8353, an orally administered ERK1/2 inhibitor, in patients with advanced solid tumors. JCI Insight 2018; 3 (4).Google Scholar
Sullivan, RJ, Infante, JR, Janku, F et al. First-in-class ERK1/2 inhibitor ulixertinib (BVD-523) in patients with MAPK mutant advanced solid tumors: Results of a phase I dose-escalation and expansion study. Cancer Discov 2018; 8 (2): 184–195.Google Scholar
Desai, J, Gan, H, Barrow, C et al. Phase I, open-label, dose-escalation/dose-expansion study of lifirafenib (BGB-283), an RAF family kinase inhibitor, in patients with solid tumors. J Clin Oncol 2020; 38 (19): 2140–2150.Google Scholar
Pulciani, S, Santos, E, Lauver, AV et al. Oncogenes in solid human tumours. Nature 1982; 300 (5892): 539–542.Google Scholar
Martin-Zanca, D, Hughes, SH, Barbacid, M. A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences. Nature 1986; 319 (6056): 743–748.Google Scholar
Valent, A, Danglot, G, Bernheim, A. Mapping of the tyrosine kinase receptors trkA (NTRK1), trkB (NTRK2) and trkC(NTRK3) to human chromosomes 1q22, 9q22 and 15q25 by fluorescence in situ hybridization. Eur J Hum Genet 1997; 5 (2): 102–104.Google Scholar
Chao, MV. Neurotrophins and their receptors: A convergence point for many signalling pathways. Nat Rev Neurosci 2003; 4 (4): 299–309.Google Scholar
Stransky, N, Cerami, E, Schalm, S et al. The landscape of kinase fusions in cancer. Nat Commun 2014; 5: 4846.Google Scholar
Cocco, E, Scaltriti, M, Drilon, A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol 2018; 15 (12): 731–747.Google Scholar
Tognon, C GM, Kenward, E, Kay, R, Morrison, K, Sorensen, PH. The chimeric protein tyrosine kinase ETV6-NTRK3 requires both Ras-Erk1/2 and PI3-kinase-Akt signaling for fibroblast transformation. Cancer Res 2001; 61 (24): 8909–8916.Google Scholar
Ozono, K, Ohishi, Y, Onishi, H et al. Brain-derived neurotrophic factor/tropomyosin-related kinase B signaling pathway contributes to the aggressive behavior of lung squamous cell carcinoma. Lab Invest 2017; 97 (11): 1332–1342.Google Scholar
Greco, A, Miranda, C, Pierotti, MA. Rearrangements of NTRK1 gene in papillary thyroid carcinoma. Mol Cell Endocrinol 2010; 321 (1): 44–49.Google Scholar
Shah, N, Lankerovich, M, Lee, H et al. Exploration of the gene fusion landscape of glioblastoma using transcriptome sequencing and copy number data. BMC Genomics 2013; 14: 818.Google Scholar
Ross, JS, Wang, K, Gay, L et al. New routes to targeted therapy of intrahepatic cholangiocarcinomas revealed by next-generation sequencing. Oncologist 2014; 19 (3): 235–242.Google Scholar
Marchio, C, Scaltriti, M, Ladanyi, M et al. ESMO recommendations on the standard methods to detect NTRK fusions in daily practice and clinical research. Ann Oncol 2019; 30 (9): 1417–1427.Google Scholar
Vaishnavi, A, Capelletti, M, Le, AT et al. Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. Nat Med 2013; 19 (11): 1469–1472.Google Scholar
Farago, AF, Taylor, MS, Doebele, RC et al. Clinicopathologic features of non-small-cell lung cancer harboring an NTRK gene fusion. JCO Precis Oncol 2018; 2018.Google Scholar
Okamura, K, Harada, T, Wang, S et al. Expression of TrkB and BDNF is associated with poor prognosis in non-small cell lung cancer. Lung Cancer 2012; 78 (1): 100–106.Google Scholar
Ekman, S. How selecting best therapy for metastatic NTRK fusion-positive non-small cell lung cancer? Transl Lung Cancer Res 2020; 9 (6): 2535–2544.Google Scholar
Drilon, A, Laetsch, TW, Kummar, S et al. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med 2018; 378 (8): 731–739.Google Scholar
Hong, DS, DuBois, SG, Kummar, S et al. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol 2020; 21 (4): 531–540.Google Scholar
Drilon, A MGV, Patel, J, et al. Efficacy and safety of larotrectinib in patients with tropomyosin receptor kinase (TRK) fusion lung cancer. Ann Oncol 2020; 31 (suppl. 4): S754–S840.Google Scholar
Haratake, N, Seto, T. fusion-positive non–small-cell, NTRK lung cancer: The diagnosis and targeted therapy. Clin Lung Cancer 2021; 22 (1): 1–5.Google Scholar
Doebele, RC, Drilon, A, Paz-Ares, L et al. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: Integrated analysis of three phase 1–2 trials. Lancet Oncol 2020; 21 (2): 271–282.Google Scholar
Drilon, A, Paz-Ares, L, Doebele, RC et al. 543P Entrectinib in NTRK fusion-positive NSCLC: Updated integrated analysis of STARTRK-2, STARTRK-1 and ALKA-372–001. Ann Oncol 2020; 31: S474–S475.Google Scholar
Russo, M, Misale, S, Wei, G et al. Acquired resistance to the TRK inhibitor entrectinib in colorectal cancer. Cancer Discov 2016; 6 (1): 36–44.Google Scholar
Drilon, A, Li, G, Dogan, S et al. What hides behind the MASC: Clinical response and acquired resistance to entrectinib after ETV6-NTRK3 identification in a mammary analogue secretory carcinoma (MASC). Ann Oncol 2016; 27 (5): 920–926.Google Scholar
Doebele, RC DR, Drilon, A, et al. Genomic landscape of entrectinib resistance from ctDNA analysis in STARTRK-2. Ann Oncol 2019;30; 30 (suppl. 5): v865.Google Scholar
Fuse, MJ, Okada, K, Oh-Hara, T et al. Mechanisms of resistance to NTRK inhibitors and therapeutic strategies in NTRK1-rearranged cancers. Mol Cancer Ther 2017; 16 (10): 2130–2143.Google Scholar
Russo, A, Cardona, AF, Caglevic, C et al. Overcoming TKI resistance in fusion-driven NSCLC: New generation inhibitors and rationale for combination strategies. Transl Lung Cancer Res 2020; 9 (6): 2581–2598.Google Scholar
Combating acquired, Poh A. TRK inhibitor resistance. Cancer Discov 2019; 9 (6): 684–685.Google Scholar
Hyman, D, Kummar, S, Farago, A et al. Abstract CT127: Phase I and expanded access experience of LOXO-195 (BAY 2731954), a selective next-generation TRK inhibitor (TRKi). Cancer Res 2019; 79 (13 suppl.): CT127.Google Scholar
Drilon, A, Ou, SI, Cho, BC et al. Repotrectinib (TPX-0005) is a next-generation ROS1/TRK/ALK inhibitor that potently inhibits ROS1/TRK/ALK solvent- front mutations. Cancer Discov 2018; 8 (10): 1227–1236.Google Scholar
Drilon, AZD, Zhai, D, Deng, W et al. Repotrectinib, a next generation TRK inhibitor, overcomes TRK resistance mutations including solvent front, gatekeeper and compound mutations. Cancer Res 2019; 79 (13 suppl.): 442.Google Scholar
Cho, BC DR, Lin, JJ, et al. Phase 1/2 TRIDENT-1 study of repotrectinib in patients with ROS1+ or NTRK+ advanced solid tumors. International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer. Abstract MA11.07. 2021 (virtual).Google Scholar
Zhou, C, Zhou, H, Yan, B. Innovent and AnHeart announce interim data from phase 2 trial (TRUST study) of taletrectinib in ROS1-positive NSCLC at the CSCO 2021 Annual Meeting. Innovent Biologics Inc., Suzhou, September 27, 2021.Google Scholar
Wieduwilt, MJ, Moasser, MM. The epidermal growth factor receptor family: Biology driving targeted therapeutics. Cell Mol Life Sci 2008; 65 (10): 1566–1584.Google Scholar
Yarden, Y. Biology of HER2 and its importance in breast cancer. Oncology 2001; 61 (suppl. 2): 1–13.Google Scholar
Nakamura, H, Saji, H, Ogata, A et al. Correlation between encoded protein overexpression and copy number of the HER2 gene with survival in non-small cell lung cancer. Intern J Cancer 2003; 103 (1): 61–66.Google Scholar
Zhao, J, Xia, Y. Targeting HER2 alterations in non–small-cell lung cancer: A comprehensive review. JCO Precis Oncol 2020 (4): 411–425.Google Scholar
Liu, L, Shao, X, Gao, W et al. The role of human epidermal growth factor receptor 2 as a prognostic factor in lung cancer: A meta-analysis of published data. J Thorac Oncol 2010; 5 (12): 1922–1932.Google Scholar
Yoshizawa, A, Sumiyoshi, S, Sonobe, M et al. HER2 status in lung adenocarcinoma: A comparison of immunohistochemistry, fluorescence in situ hybridization (FISH), dual-ISH, and gene mutations. Lung Cancer 2014; 85 (3): 373–378.Google Scholar
Greulich, H, Kaplan, B, Mertins, P et al. Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ERBB2. Proc Natl Acad Sci USA 2012; 109 (36): 14476–14481.Google Scholar
Patil, T, Mushtaq, R, Marsh, S et al. Clinicopathologic characteristics, treatment outcomes, and acquired resistance patterns of atypical EGFR mutations and HER2 alterations in stage IV non-small-cell lung cancer. Clin Lung Cancer 2020; 21 (3): e191–e204.Google Scholar
Arcila, ME, Chaft, JE, Nafa, K et al. Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin Cancer Res 2012; 18 (18): 4910–4918.Google Scholar
Mazières, J, Barlesi, F, Filleron, T et al. Lung cancer patients with HER2 mutations treated with chemotherapy and HER2-targeted drugs: Results from the European EUHER2 cohort. Ann Oncol 2016; 27 (2): 281–286.Google Scholar
De Grève, J, Moran, T, Graas, M-P et al. Phase II study of afatinib, an irreversible ErbB family blocker, in demographically and genotypically defined lung adenocarcinoma. Lung Cancer 2015; 88 (1): 63–69.Google Scholar
Dziadziuszko, R, Smit, EF, Dafni, U et al. Afatinib in NSCLC With HER2 mutations: Results of the prospective, open-label phase II NICHE trial of European Thoracic Oncology Platform (ETOP). J Thorac Oncol 2019; 14 (6): 1086–1094.Google Scholar
Kris, MG, Camidge, DR, Giaccone, G et al. Targeting HER2 aberrations as actionable drivers in lung cancers: phase II trial of the pan-HER tyrosine kinase inhibitor dacomitinib in patients with HER2-mutant or amplified tumors. Ann Oncol 2015; 26 (7): 1421–1427.Google Scholar
Hyman, DM, Piha-Paul, SA, Won, H et al. HER kinase inhibition in patients with HER2- and HER3-mutant cancers. Nature 2018; 554 (7691): 189–194.Google Scholar
Gandhi, L, Besse, B, Mazieres, J et al. MA04.02 neratinib ± temsirolimus in HER2-mutant lung cancers: An international, randomized phase II study. J Thorac Oncol 2017; 12 (1 suppl.): S358–S359.Google Scholar
Kim, TM, Lee, K-W, Oh, D-Y et al. Phase 1 studies of poziotinib, an irreversible pan-HER tyrosine kinase inhibitor in patients with advanced solid tumors. Cancer Res Treat 2018; 50 (3): 835–842.Google Scholar
Elamin, YY, Robichaux, JP, Carter, BW et al. Poziotinib for patients with HER2 exon 20 Mutant non-small-cell lung cancer: Results from a phase II trial. J Clin Oncol 2021: JCO2101113.Google Scholar
Socinski, MA, Cornelissen, R, Garassino, MC et al. LBA60 ZENITH20, a multinational, multi-cohort phase II study of poziotinib in NSCLC patients with EGFR or HER2 exon 20 insertion mutations. Ann Oncol 2020; 31: S1188.Google Scholar
Riudavets, M, Sullivan, I, Abdayem, P et al. Targeting HER2 in non-small-cell lung cancer (NSCLC): A glimpse of hope? An updated review on therapeutic strategies in NSCLC harbouring HER2 alterations. ESMO Open 2021; 6 (5): 100260.Google Scholar
Wang, Y, Jiang, T, Qin, Z et al. HER2 exon 20 insertions in non-small-cell lung cancer are sensitive to the irreversible pan-HER receptor tyrosine kinase inhibitor pyrotinib. Ann Oncol 2019; 30 (3): 447–455.Google Scholar
Zhou, C, Li, X, Wang, Q et al. Pyrotinib in HER2-mutant advanced lung adenocarcinoma after platinum-based chemotherapy: A multicenter, open-label, single-arm, phase II study. J Clin Oncol 2020; 38 (24): 2753–2761.Google Scholar
Kinoshita, I, Goda, T, Watanabe, K et al. A phase II study of trastuzumab monotherapy in pretreated patients with non-small cell lung cancers (NSCLCs) harboring HER2 alterations: HOT1303-B trial. Ann Oncol 2018; 29: viii540.Google Scholar
Gatzemeier, U, Groth, G, Butts, C et al. Randomized phase II trial of gemcitabine-cisplatin with or without trastuzumab in HER2-positive non-small-cell lung cancer. Ann Oncol 2004; 15 (1): 19–27.Google Scholar
Hainsworth, JD, Meric-Bernstam, F, Swanton, C et al. Targeted therapy for advanced solid tumors on the basis of molecular profiles: Results from MyPathway, an open-label, phase IIa multiple basket study. J Clin Oncol 2018; 36 (6): 536–542.Google Scholar
Hotta, K, Aoe, K, Kozuki, T et al. A phase II study of trastuzumab emtansine in HER2-positive non-small cell lung cancer. J Thorac Oncol 2018; 13 (2): 273–279.Google Scholar
Li, BT, Shen, R, Buonocore, D et al. Ado-trastuzumab emtansine for patients with HER2-mutant lung cancers: Results from a phase II basket trial. J Clin Oncol 2018; 36 (24): 2532–2537.Google Scholar
Ogitani, Y, Aida, T, Hagihara, K et al. DS-8201a, a novel HER2-targeting ADC with a novel DNA topoisomerase I inhibitor, demonstrates a promising antitumor efficacy with differentiation from T-DM1. Clin Cancer Res 2016; 22 (20): 5097–5108.Google Scholar
Tsurutani, J, Iwata, H, Krop, I et al. Targeting HER2 with trastuzumab deruxtecan: A dose-expansion, phase I study in multiple advanced solid tumors. Cancer Discov 2020; 10 (5): 688–701.Google Scholar
Li, BT, Smit, EF, Goto, Y et al. Trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer. N Engl J Med 2021; 386 (3): 241–251.Google Scholar
Cheng, H, Liu, P, Ohlson, C et al. PIK3CA(H1047R)- and Her2-initiated mammary tumors escape PI3K dependency by compensatory activation of MEK-ERK signaling. Oncogene 2016; 35 (23): 2961–2970.Google Scholar
Zeng, J, Ma, W, Young, RB et al. Targeting HER2 genomic alterations in non-small cell lung cancer. J Nat Cancer Center 2021; 1 (2): 58–73.Google Scholar
Song, Z, Lv, D, Chen, S et al. Efficacy and resistance of afatinib in Chinese non-small cell lung cancer patients with HER2 alterations: A multicenter retrospective study. Front Oncol 2021; 11: 657283.Google Scholar
Li, BT, Michelini, F, Misale, S et al. HER2-mediated internalization of cytotoxic agents in ERBB2 amplified or mutant lung cancers. Cancer Discov 2020; 10 (5): 674–687.Google Scholar
Robichaux, JP, Elamin, YY, Tan, Z et al. Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer. Nat Med 2018; 24 (5): 638–646.Google Scholar
D’Amico, L, Menzel, U, Prummer, M et al. A novel anti-HER2 anthracycline-based antibody-drug conjugate induces adaptive anti-tumor immunity and potentiates PD-1 blockade in breast cancer. J Immunother Cancer 2019; 7 (1): 16.Google Scholar
Lindeman, NI, Cagle, PT, Aisner, DL et al. Updated Molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: Guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. Arch Pathol Lab Med 2018; 142 (3): 321–346.Google Scholar
Sholl, LM, Weremowicz, S, Gray, SW et al. Combined use of ALK immunohistochemistry and FISH for optimal detection of ALK-rearranged lung adenocarcinomas. J Thorac Oncol 2013; 8 (3): 322–328.Google Scholar
Go, H, Jung, YJ, Kang, HW et al. Diagnostic method for the detection of KIF5B-RET transformation in lung adenocarcinoma. Lung Cancer 2013; 82 (1): 44–50.Google Scholar
Yoshida, A, Tsuta, K, Wakai, S et al. Immunohistochemical detection of ROS1 is useful for identifying ROS1 rearrangements in lung cancers. Mod Pathol 2014; 27 (5): 711–720.Google Scholar
Boyle, TA, Masago, K, Ellison, KE et al. ROS1 immunohistochemistry among major genotypes of non-small-cell lung cancer. Clin Lung Cancer 2015; 16 (2): 106–111.Google Scholar
Mescam-Mancini, L, Lantuejoul, S, Moro-Sibilot, D et al. On the relevance of a testing algorithm for the detection of ROS1-rearranged lung adenocarcinomas. Lung Cancer 2014; 83 (2): 168–173.Google Scholar
Chen, YF, Hsieh, MS, Wu, SG et al. Clinical and the prognostic characteristics of lung adenocarcinoma patients with ROS1 fusion in comparison with other driver mutations in East Asian populations. J Thorac Oncol 2014; 9 (8): 1171–1179.Google Scholar
Lee, SE, Lee, B, Hong, M et al. Comprehensive analysis of RET and ROS1 rearrangement in lung adenocarcinoma. Mod Pathol 2015; 28 (4): 468–479.Google Scholar
Matter, MS, Chijioke, O, Savic, S et al. Narrative review of molecular pathways of kinase fusions and diagnostic approaches for their detection in non-small cell lung carcinomas. Transl Lung Cancer Res 2020; 9 (6): 2645–2655.Google Scholar
Kitamura, A, Hosoda, W, Sasaki, E et al. Immunohistochemical detection of EGFR mutation using mutation-specific antibodies in lung cancer. Clin Cancer Res 2010; 16 (13): 3349–3355.Google Scholar
Ilie, M, Long, E, Hofman, V et al. Diagnostic value of immunohistochemistry for the detection of the BRAFV600E mutation in primary lung adenocarcinoma Caucasian patients. Ann Oncol 2013; 24 (3): 742–748.Google Scholar
Sasaki, H, Shimizu, S, Tani, Y et al. Usefulness of immunohistochemistry for the detection of the BRAF V600E mutation in Japanese lung adenocarcinoma. Lung Cancer 2013; 82 (1): 51–54.Google Scholar
Schuler, M, Berardi, R, Lim, WT et al. Molecular correlates of response to capmatinib in advanced non-small-cell lung cancer: clinical and biomarker results from a phase I trial. Ann Oncol 2020; 31 (6): 789–797.Google Scholar
Spigel, DR, Edelman, MJ, O’Byrne, K et al. Results From the phase III randomized trial of onartuzumab plus erlotinib versus erlotinib in previously treated stage IIIB or IV non-small-cell lung cancer: METLung. J Clin Oncol 2017; 35 (4): 412–420.Google Scholar
Neal, JW, Dahlberg, SE, Wakelee, HA et al. Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): A randomised, controlled, open-label, multicentre, phase 2 trial. Lancet Oncol 2016; 17 (12): 1661–1671.Google Scholar
Guo, R, Berry, LD, Aisner, DL et al. MET IHC is a poor screen for MET amplification or MET exon 14 mutations in lung adenocarcinomas: Data from a tri-institutional cohort of the Lung Cancer Mutation Consortium. J Thorac Oncol 2019; 14 (9): 1666–1671.Google Scholar
Ricciardi, GR, Russo, A, Franchina, T et al. NSCLC and HER2: Between lights and shadows. J Thorac Oncol 2014; 9 (12): 1750–1762.Google Scholar
Yoshizawa, A, Sumiyoshi, S, Sonobe, M et al. HER2 status in lung adenocarcinoma: A comparison of immunohistochemistry, fluorescence in situ hybridization (FISH), dual-ISH, and gene mutations. Lung Cancer 2014; 85 (3): 373–378.Google Scholar
Rolfo, C, Russo, A. HER2 mutations in non-small cell lung cancer: A Herculean effort to hit the target. Cancer Discov 2020; 10 (5): 643–645.Google Scholar
Hotta, K, Aoe, K, Kozuki, T et al. A phase II study of trastuzumab emtansine in HER2-positive non-small cell lung cancer. J Thorac Oncol 2018; 13 (2): 273–279.Google Scholar
Peters, S, Stahel, R, Bubendorf, L et al. Trastuzumab emtansine (T-DM1) in patients with previously treated HER2-overexpressing metastatic non-small cell lung cancer: Efficacy, safety, and biomarkers. Clin Cancer Res 2019; 25 (1): 64–72.Google Scholar
Wang, R, Hu, H, Pan, Y et al. RET fusions define a unique molecular and clinicopathologic subtype of non-small-cell lung cancer. J Clin Oncol 2012; 30 (35): 4352–4359.Google Scholar
Rebuzzi, SE, Zullo, L, Rossi, G et al. Novel emerging molecular targets in non-small cell lung cancer. Int J Mol Sci 2021; 22 (5).Google Scholar
Hsiao, SJ, Zehir, A, Sireci, AN et al. Detection of tumor NTRK gene fusions to identify patients who may benefit from tyrosine kinase (TRK) inhibitor therapy. J Mol Diagn 2019; 21 (4): 553–571.Google Scholar
Vallée, A, Herbreteau, G, Sagan, C et al. 1130P anchored multiplex PCR-based targeted sequencing for the detection of fusion transcripts in FFPE samples of non-small cell lung cancer patients. Ann Oncol 2021; 32.Google Scholar
Jennings, LJ, Arcila, ME, Corless, C et al. Guidelines for validation of next-generation sequencing-based oncology panels: A joint consensus recommendation of the Association for Molecular Pathology and College of American Pathologists. J Mol Diagn 2017; 19 (3): 341–365.Google Scholar
Benayed, R, Offin, M, Mullaney, K et al. High yield of RNA sequencing for targetable kinase fusions in lung adenocarcinomas with no mitogenic driver alteration detected by DNA sequencing and low tumor mutation burden. Clin Cancer Res 2019; 25 (15): 4712–4722.Google Scholar
Oxnard, GR, Paweletz, CP, Kuang, Y et al. Noninvasive detection of response and resistance in EGFR-mutant lung cancer using quantitative next-generation genotyping of cell-free plasma DNA. Clin Cancer Res 2014; 20 (6): 1698–1705.Google Scholar
Garcia, J, Wozny, AS, Geiguer, F et al. Profiling of circulating tumor DNA in plasma of non-small cell lung cancer patients, monitoring of epidermal growth factor receptor p.T790M mutated allelic fraction using beads, emulsion, amplification, and magnetics companion assay and evaluation in future application in mimicking circulating tumor cells. Cancer Med 2019; 8 (8): 3685–3697.Google Scholar
Leighl, NB, Page, RD, Raymond, VM et al. Clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer. Clin Cancer Res 2019; 25 (15): 4691–4700.Google Scholar
Aggarwal, C, Thompson, JC, Black, TA et al. Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer. JAMA Oncol 2019; 5 (2): 173–180.Google Scholar
Park, S, Lee, JC, Choi, CM. Clinical applications of liquid biopsy in non-small cell lung cancer patients: Current status and recent advances in clinical practice. J Clin Med 2021; 10 (11).Google Scholar
Maheswaran, S, Sequist, LV, Nagrath, S et al. Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 2008; 359 (4): 366–377.Google Scholar
Guibert, N, Pradines, A, Farella, M et al. Monitoring KRAS mutations in circulating DNA and tumor cells using digital droplet PCR during treatment of KRAS-mutated lung adenocarcinoma. Lung Cancer 2016; 100: 1–4.Google Scholar
Mondaca, S, Lebow, ES, Namakydoust, A et al. Clinical utility of next-generation sequencing-based ctDNA testing for common and novel ALK fusions. Lung Cancer 2021; 159: 66–73.Google Scholar
Odegaard, JI, Vincent, JJ, Mortimer, S et al. Validation of a plasma-based comprehensive cancer genotyping assay utilizing orthogonal tissue- and plasma-based methodologies. Clin Cancer Res 2018; 24 (15): 3539–3549.Google Scholar
Thompson, JC, Yee, SS, Troxel, AB et al. Detection of therapeutically targetable driver and resistance mutations in lung cancer patients by next-generation sequencing of cell-free circulating tumor DNA. Clin Cancer Res 2016; 22 (23): 5772–5782.Google Scholar
Hochmair, MJ, Buder, A, Schwab, S et al. Liquid-biopsy-based identification of EGFR T790M mutation-mediated resistance to afatinib treatment in patients with advanced EGFR mutation-positive NSCLC, and subsequent response to osimertinib. Target Oncol 2019; 14 (1): 75–83.Google Scholar
Del Re, M, Crucitta, S, Gianfilippo, G et al. Understanding the mechanisms of resistance in EGFR-positive NSCLC: From tissue to liquid biopsy to guide treatment strategy. Int J Mol Sci 2019; 20 (16).Google Scholar
Iacovino, M, Ciaramella, V, Paragliola, F et al. Use of liquid biopsy in monitoring therapeutic resistance in EGFR oncogene addicted NSCLC. Explor Target Anti-tumor Ther 2020; 1 (6): 391–400.Google Scholar
Lee, M, Patel, D, Jofre, S et al. Large cell neuroendocrine carcinoma transformation as a mechanism of acquired resistance to osimertinib in non-small cell lung cancer: Case report and literature review. Clin Lung Cancer 2021.Google Scholar
Bettegowda, C, Sausen, M, Leary, RJ et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med 2014; 6 (224): 224ra224.Google Scholar
Douillard, JY, Ostoros, G, Cobo, M et al. Gefitinib treatment in EGFR mutated caucasian NSCLC: Circulating-free tumor DNA as a surrogate for determination of EGFR status. J Thorac Oncol 2014; 9 (9): 1345–1353.Google Scholar
Thress, KS, Brant, R, Carr, TH et al. EGFR mutation detection in ctDNA from NSCLC patient plasma: A cross-platform comparison of leading technologies to support the clinical development of AZD9291. Lung Cancer 2015; 90 (3): 509–515.Google Scholar
Remon, J, Caramella, C, Jovelet, C et al. Osimertinib benefit in EGFR-mutant NSCLC patients with T790M-mutation detected by circulating tumour DNA. Ann Oncol 2017; 28 (4): 784–790.Google Scholar
Luo, J, Shen, L, Zheng, D. Diagnostic value of circulating free DNA for the detection of EGFR mutation status in NSCLC: A systematic review and meta-analysis. Sci Rep 2014; 4: 6269.Google Scholar
Guo, R, Luo, J, Chang, J et al. MET-dependent solid tumours – Molecular diagnosis and targeted therapy. Nat Rev Clin Oncol 2020; 17 (9): 569–587.Google Scholar
Paweletz, CP, Sacher, AG, Raymond, CK et al. Bias-corrected targeted next-generation sequencing for rapid, multiplexed detection of actionable alterations in cell-free DNA from advanced lung cancer patients. Clin Cancer Res 2016; 22 (4): 915–922.Google Scholar
Fleischhacker, M, Schmidt, B. Circulating nucleic acids (CNAs) and cancer – A survey. Biochim Biophys Acta 2007; 1775 (1): 181–232.Google Scholar
Guo, N, Lou, F, Ma, Y et al. Circulating tumor DNA detection in lung cancer patients before and after surgery. Sci Rep 2016; 6: 33519.Google Scholar
Chen, K, Zhang, J, Guan, T et al. Comparison of plasma to tissue DNA mutations in surgical patients with non-small cell lung cancer. J Thorac Cardiovasc Surg 2017; 154 (3): 1123–1131 e1122.Google Scholar
- 2
- Cited by