Circumventing cancer drug resistance in the era of personalized medicine

LA Garraway, PA Jänne - Cancer discovery, 2012 - AACR
Cancer discovery, 2012AACR
All successful cancer therapies are limited by the development of drug resistance. The
increase in the understanding of the molecular and biochemical bases of drug efficacy has
also facilitated studies elucidating the mechanism (s) of drug resistance. Experimental
approaches that can help predict the eventual clinical drug resistance, coupled with the
evolution of systematic genomic and proteomic technologies, are rapidly identifying novel
resistance mechanisms. In this review, we provide a historical background on drug …
Abstract
All successful cancer therapies are limited by the development of drug resistance. The increase in the understanding of the molecular and biochemical bases of drug efficacy has also facilitated studies elucidating the mechanism(s) of drug resistance. Experimental approaches that can help predict the eventual clinical drug resistance, coupled with the evolution of systematic genomic and proteomic technologies, are rapidly identifying novel resistance mechanisms. In this review, we provide a historical background on drug resistance and a framework for understanding the common ways by which cancers develop resistance to targeted therapies. We further discuss advantages and disadvantages of experimental strategies that can be used to identify drug resistance mechanism(s).
Significance: Increased knowledge of drug resistance mechanisms will aid in the development of effective therapies for patients with cancer. We provide a summary of current knowledge on drug resistance mechanisms and experimental strategies to identify and study additional drug resistance pathways. Cancer Discovery; 2(3); 214–26. ©2012 AACR.
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