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Targeting the epigenome in malignant melanoma: Facts, challenges and therapeutic promises

I Anestopoulos1, S Kyriakou1, V Tragkola1

  • 1Department of Cancer Genetics, Therapeutics & Ultrastructural Pathology, The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus.

Pharmacology & Therapeutics
|October 25, 2022
PubMed

Insights

This review explores epigenetic alterations in malignant melanoma, focusing on how targeting these changes with drugs can overcome drug resistance and improve patient outcomes for this lethal skin cancer.

Area of Science:

  • Oncology
  • Epigenetics
  • Dermatology

Background:

  • Malignant melanoma is a deadly skin cancer with poor survival rates, especially in advanced stages.
  • Acquired drug resistance limits the effectiveness of current melanoma treatments.
  • Epigenetic alterations, including DNA methylation and histone modifications, alongside genetic factors, drive melanoma development and progression.

Purpose of the Study:

  • To review current melanoma therapeutic options.
  • To highlight the role of epigenetic alterations in melanoma.
  • To discuss how epigenetic drugs can reverse aberrant phenotypes and combat drug resistance.

Main Methods:

  • Literature review of current therapeutic strategies for malignant melanoma.
  • Analysis of distinct epigenetic alterations (DNA methylation, histone modifications, non-coding RNAs) in melanoma.
  • Examination of single and combinatorial therapeutic approaches using epigenetic drug compounds.

Main Results:

  • Epigenetic modifications are crucial in melanoma onset, progression, and drug resistance.
  • Reversal of epigenetic alterations using specific drug compounds can restore normal cellular phenotypes.
  • Epigenetic drugs show potential in overcoming resistance to targeted therapies and immune checkpoint inhibitors.

Conclusions:

  • Targeting the epigenome offers a promising strategy to enhance melanoma treatment efficacy.
  • Epigenetic therapies, alone or in combination, can combat drug resistance in malignant melanoma.
  • Development of novel epigenetic drugs is essential for improving outcomes in advanced melanoma.
Keywords:
Cancer therapeuticsDNA methylationEpigenetic drugsEpigeneticsHistone modificationsMalignant melanomaNon-coding RNAs

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