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SECTION 2
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THE TRANSLATION OF BIOLOGY TO THE CLINIC
By
Yvette Drew, Newcastle University,
Timothy A Yap, Royal Marsden NHS Foundation Trust and The Institute of Cancer Research,
Stan B Kaye, Royal Marsden Hospital
This chapter discusses the results of recent clinical trials of polyadenosine diphosphate-ribose polymerase (PARP) inhibitors, either as single agents or in combination with chemotherapy, and considers the future role of PARP inhibitors in the treatment of cancer. PARP-1 has shown to regulate gene transcription, mediate p53-regulated apoptosis and initiate necrotic cell death in response to extensive DNA damage such as that occurring after myocardial infarction, stroke and septic shock, suggesting that there may be wider clinical applications for inhibitors of PARP-1. BRCA1/2 mutations account for the majority of hereditary breast and ovarian cancers but this represents only 5-15% of all ovarian and breast cancer cases. PARP inhibitors were originally developed not for single-agent use but to enhance the cytotoxicity of chemotherapy. A crucial recent development has been that, in addition to BRCA-mutated cancers, a role for PARP inhibitors is emerging in sporadic cancers, in particular high-grade serous ovarian carcinomas (HGSOC).
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