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Epigenetic Therapy for Cancer Stem Cells

A New Arrow in the Quiver

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Abstract

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.

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Acknowledgements

The authors sincerely thank Prof. H. A Ranganath for his critical reading of the manuscript and useful suggestions. The authors also acknowledge all the support from the Centre for Human Genetics during the preparation of this manuscript. All the figures in the article have been created using the BioRender software.

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Authors and Affiliations

  1. Centre for Human Genetics, Biotech Park, Electronics City Phase 1, Bengaluru, 560 100, India

    Akshatha E. Nagarkatte & Prathibha Ranganathan

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  1. Akshatha E. Nagarkatte
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  2. Prathibha Ranganathan
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Correspondence to Akshatha E. Nagarkatte or Prathibha Ranganathan.

Additional information

Akshatha E. Nagarkatte has completed her MSc in Human Disease Genetics from the Centre for Human Genetics. Her areas of interest include cancer biology, epigenetics, and cytogenetics. She aspires to pursue PhD in the field of cancer biology.

Prathibha Ranganthan heads the Cancer Lab at the Centre for Human Genetics. She is interested in understanding the molecular basis of chemoresistance in cancer. Her group works on elucidating the signaling, epigenetic, and gene expression changes during the development of resistance in various models of cancer.

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Nagarkatte, A.E., Ranganathan, P. Epigenetic Therapy for Cancer Stem Cells. Reson 28, 697–717 (2023). https://doi.org/10.1007/s12045-023-1600-x

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  • DOI: https://doi.org/10.1007/s12045-023-1600-x

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