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The role of cancer stem cells in tumor heterogeneity and resistance to therapy

Abstract

Cancer is a heterogenous disease displaying marked inter- and intra-tumoral diversity. The existence of cancer stem cells (CSCs) has been experimentally demonstrated in a number of cancer types as a subpopulation of tumor cells that drives the tumorigenic and metastatic properties of the entire cancer. Thus, eradication of the CSC population is critical for the complete ablation of a tumor. This is, however, confounded by the inherent resistance of CSCs to standard anticancer therapies, eventually leading to the outgrowth of resistant tumor cells and relapse in patients. The cellular mechanisms of therapy resistance in CSCs are ascribed to several factors including a state of quiescence, an enhanced DNA damage response and active repair mechanisms, up-regulated expression of drug efflux transporters, as well as the activation of pro-survival signaling pathways and inactivation of apoptotic signaling. Understanding the mechanisms underlying the acquisition of resistance to therapy may hold the key to targeting the CSC population.

Type Journal
ISBN 1205-7541 (Electronic) 0008-4212 (Linking)
Authors Konrad, C. V.; Murali, R.; Varghese, B. A.; Nair, R.
Responsible Garvan Author (missing name)
Publisher Name CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
Published Date 2017-01-31
Published Volume 95
Published Issue 1
Published Pages 1-15
Status Published in-print
DOI 10.1139/cjpp-2016-0079
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/27925473