Cancer drug resistance continues to be a major impediment in medical oncology. Clinically, resistance can arise prior to or as a result of cancer therapy. In this review, we discuss different mechanisms adapted by cancerous cells to resist treatment, including alteration in drug transport and metabolism, mutation and amplification of drug targets, as well as genetic rewiring which can lead to impaired apoptosis. Tumor heterogeneity may also contribute to resistance, where small subpopulations of cells may acquire or stochastically already possess some of the features enabling them to emerge under selective drug pressure. Making the problem even more challenging, some of these resistance pathways lead to multidrug resistance, generating an even more difficult clinical problem to overcome. We provide examples of these mechanisms and some insights into how understanding these processes can influence the next generation of cancer therapies.
Keywords: origin of cancer, multidrug resistance, drug metabolism, drug transporters, oncogene addiction, microenvironment, collateral sensitivity, synthetic lethality
Citation: Zahreddine H and Borden KLB (2013) Mechanisms and insights into drug resistance in cancer. Front. Pharmacol. 4:28. doi: 10.3389/fphar.2013.00028
Received: 31 December 2012; Paper pending published: 17 January 2013;
Accepted: 25 February 2013; Published online: 14 March 2013.
Edited by:Gerald Batist, McGill University, Canada
Copyright: © 2013 Zahreddine and Borden. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Katherine L. B. Borden, Department of Pathology and Cell Biology, Institute of Research in Immunology and Cancer, Université de Montréal, Montreal, QC, Canada H3T 1J4. e-mail: email@example.com