Epigenetic Modulators and Immunotherapy in Malignant Melanoma

Ioannis Anestopoulos1, Sotiris Kyriakou1, Maria Deligiorgi2

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

Oncology Research
|July 25, 2026
PubMed

Insights

Epigenetic alterations drive melanoma progression and resistance to immunotherapy. Epigenetic drugs, combined with immune checkpoint inhibitors, show promise in overcoming this resistance and improving patient outcomes.

Area of Science:

  • Oncology
  • Immunology
  • Epigenetics

Background:

  • Melanoma mortality remains high despite targeted and immune therapies, largely due to drug resistance.
  • Epigenetic alterations, including DNA methylation and non-coding RNA changes, are implicated in melanoma development and therapeutic resistance.

Purpose of the Study:

  • To review the role of epigenetic mechanisms in melanoma progression and resistance to immunotherapy.
  • To explore the potential of epigenetic drugs in combination with immune checkpoint inhibitors to overcome drug resistance.

Main Methods:

  • Literature review of epigenetic mechanisms in melanoma.
  • Analysis of melanoma immune microenvironment and immunosuppressive factors.
  • Examination of drug resistance mechanisms related to epigenetic deregulation.
  • Evaluation of epigenetic drugs and emerging technologies for melanoma treatment.

Main Results:

  • Epigenetic dysregulation contributes significantly to melanoma pathophysiology and resistance to immune checkpoint inhibitors.
  • Epigenetic drugs can potentially reverse resistance to immune checkpoint inhibitors when used alone or in combination.
  • Emerging technologies like single-cell and spatial transcriptomics offer new avenues for clinical translation.

Conclusions:

  • Epigenetic modifications are critical drivers of melanoma progression and therapeutic resistance.
  • Combining epigenetic therapies with immune checkpoint inhibitors is a promising strategy to improve melanoma treatment outcomes.
  • Further research and technological advancements are needed for effective clinical implementation of epigenetic strategies in melanoma management.

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