Epigenetic Therapy for Cancer Stem Cells

Substantial evidence has shown that tumors can emerge from a distinct, small population of cells known as cancer stem cells (CSCs), which have a vital role in the initiation, maintenance, metastasis, drug resistance, and relapse of cancer. Hence, it is critical to identify drugs that selectively target and eliminate CSCs to induce a long-lasting therapeutic response and better patient outcomes. Modulations in epigenetic regulation contribute to cancer progression as it is crucial for both stem cell biology and chemoresistance. Polycomb group (PcG) and trithorax group (TrxG) proteins are identified as the key modulators of cellular memory that direct whether a stem cell will self-renew or differentiate. The dynamic interaction of these two groups of proteins with opposing effects on gene expression has opened up new avenues for understanding their role in tumorigenesis. Therefore, it is essential to elucidate the underlying mechanisms of aberrant epigenetic modifications, without which designing drugs becomes implausible. The existing cancer treatments like radiotherapy and chemotherapy have major limitations owing to treatment failure and recurrence of cancer. However, the application of epigenetic therapy has shown promising therapeutic results in clinical trials with its ability to reverse the aberrant epigenetic modifications that result in cancer and chemotherapy resistance. Future research aimed at developing drugs that are target specific is necessary to prevent off-target effects. To overcome the limitations of the current epidrugs, novel approaches like CRISPR/Cas9-based epigenetic editing are emerging as new hopes for targeted therapy in cancer. This article gives an overview of the till-date understanding of the role of epigenetics in cancer stem cell biology and recent developments in epigenetic therapy.