Cancer stem cell epigenetics and chemoresistance.

Cancer stem cells (CSCs) are thought to sustain cancer progression, metastasis and recurrence after therapy. There is in vitro and in vivo evidence supporting the idea that CSCs are highly chemoresistant. Epigenetic gene regulation is crucial for both stem cell biology and chemoresistance. In this review, we summarize current data on epigenetic mechanisms of chemoresistance in cancer stem cells. We propose a model integrating classical CSC pathways (Wnt, Hedgehog and Notch), epigenetic effectors (Polycomb) and drug resistance genes (ABCG2, CD44). Moreover, we analyze the potential of epigenetic drugs to reverse CSC chemoresistance. In the future, CSC epigenomic profiling could help to dissect specific chemoresistance pathways, and have a significant clinical impact for patient stratification and rational design of therapeutic regimens.