Colon cancer stem cells - From basic to clinical application

Based on cancer stem cell (CSC) concept of carcinogenesis, tumors represent complex heterogeneous organ-like systems with a hierarchical cellular organization, and only minority phenotypic subpopulations with stem-like properties possess a dual ability to self-renew indefinitely and produce all the heterogeneous cell phenotypes comprising the bulk tumor cells. Large experimental and clinical data indicate that conventional anti-cancer therapies cannot eradicate CSCs, and moreover, they usually increase their number leading to cancer recurrence and further drug resistance. In this review, several current controversies in the CSC field and recent studies, which help to shed light on their origin, are discussed. The emerging necessity for the development of complex, multimodal CSC-targeted treatment strategies, which combine conventional therapeutics with promising pathway-specific modulators, and natural compounds, which can improve the efficacy of conventional anti-cancer therapeutics and decrease their undesirable side effects is presented. Also, novel requirements and criteria necessary for evaluation of the CSC-targeted drug efficacy and relevant experimental models are discussed. (C) 2012 Elsevier Ireland Ltd. All rights reserved.