Epidrugs in cancer: mechanisms, applications, and future direction

Roshni Bibi1, Lakshmi Varshetha1, Rakshit Kamal Lahary1

  • 1Department of Biotechnology, School of Bioengineering, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, Chennai, Tamil Nadu, 603203, India.

Insights

Epigenetic modifications influence cancer development and are reversible, making them promising therapeutic targets. This review explores epidrugs like DNMTis and HDACis, their mechanisms, and clinical applications in various cancers.

Area of Science:

  • Epigenetics and Cancer Biology
  • Pharmacology and Therapeutics

Background:

  • Epigenetic modifications (DNA methylation, histone modifications, non-coding RNA regulation) are crucial in cancer initiation and progression.
  • These reversible changes offer therapeutic opportunities distinct from genetic mutations.

Purpose of the Study:

  • To review various classes of epidrugs, including DNA methyltransferase inhibitors (DNMTis), histone deacetylase inhibitors (HDACis), histone methyltransferase inhibitors (HMTis), and BET inhibitors.
  • To summarize the mechanisms of action, therapeutic potential, and clinical applications of these epidrugs across diverse cancers.
  • To address challenges and future directions for epigenetic therapies in oncology.

Main Methods:

  • Comprehensive literature review of epidrugs targeting epigenetic pathways.
  • Analysis of preclinical and clinical data on epidrug efficacy and toxicity.
  • Exploration of combination strategies with conventional therapies, immunotherapy, and targeted treatments.

Main Results:

  • Epidrugs demonstrate potential in treating solid tumors (breast, lung, colorectal, brain) and hematological malignancies (AML, multiple myeloma).
  • These drugs can reverse gene silencing, overcome drug resistance, and enhance tumor sensitivity to existing treatments.
  • Challenges include drug toxicity, off-target effects, and acquired resistance, necessitating careful management.

Conclusions:

  • Epidrugs represent a significant advancement in cancer treatment, offering novel mechanisms to control aberrant gene expression.
  • Personalized epigenetic therapy, guided by tumor-specific epigenome analysis, holds promise for tailored treatment strategies.
  • Overcoming current limitations through combination therapies and addressing toxicity are key to maximizing the clinical benefit of epigenetic approaches in cancer care.

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