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

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 which 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 anti-cancer 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.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author