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RNAi-mediated functional analysis of pathways influencing cancer cell drug resistance

Published online by Cambridge University Press:  21 May 2009

Alvin J.X. Lee ,
Richard Kolesnick  and
Charles Swanton
Alvin J.X. Lee
Affiliation:
Translational Cancer Therapeutics Laboratory, Cancer Research UK London Research Institute, London, UK.
Richard Kolesnick
Affiliation:
Laboratory of Signal Transduction, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Charles Swanton*
Affiliation:
Translational Cancer Therapeutics Laboratory, Cancer Research UK London Research Institute, London, UK. Royal Marsden NHS Foundation Trust, Breast and Drug Development Units, Downs Road, Sutton, UK.
*
*Corresponding author: Charles Swanton, Translational Cancer Therapeutics Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK. Tel: +44 20 7269 3463; Fax: +44 20 7269 3094; E-mail: charles.swanton@cancer.org.uk
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Abstract

Acquired drug resistance limits the efficacy of cytotoxics used in the management of haematological and solid tumours and is responsible for the declining clinical benefit following successive treatment regimens in metastatic cancers. Treatment failure has a major impact on quality of life and survival in advanced disease. Defining pathways of intrinsic and acquired drug resistance may provide new targets to prolong drug efficacy and time to disease progression. Predicting the intrinsic drug sensitivity of human tumours in advance of cytotoxic therapy is of paramount importance in order to limit unnecessary toxicity and optimise treatment outcome. RNA interference (RNAi) provides a powerful tool to annotate gene function and systematically define drug-resistance pathways. High-throughput screening RNAi technology has provided evidence for drug-specific resistance pathways as well as novel pathways implicated in multidrug sensitivity. The challenge is how to integrate these data with biological samples to define relevant drug-resistant pathways in vivo.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 11 , July 2009 , e15
Copyright
Copyright © Cambridge University Press 2009

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Further reading, resources and contacts

Online bioinformatics software for pathway analysis:

Downward, J. (2004) Use of RNA interference libraries to investigate oncogenic signalling in mammalian cells. Oncogene 23, 8376-8383Google Scholar
Bartz, S. and Jackson, A.L. (2005) How will RNAi facilitate drug development? Sci STKE 2005, pe39Google Scholar
http://www.genego.com/Google Scholar
Downward, J. (2004) Use of RNA interference libraries to investigate oncogenic signalling in mammalian cells. Oncogene 23, 8376-8383Google Scholar
Bartz, S. and Jackson, A.L. (2005) How will RNAi facilitate drug development? Sci STKE 2005, pe39Google Scholar
http://www.genego.com/Google Scholar