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

Malignant melanoma is the most lethal type of skin cancer with high rates of mortality. Although current treat-ment options provide a short-clinical benefit, acquired-drug resistance highlights the low 5-year survival rate among patients with advanced stage of the disease. In parallel, the involvement of an aberrant epigenetic land-scape, (e.g., alterations in DNA methylation patterns, histone modifications marks and expression of non -coding RNAs), in addition to the genetic background, has been also associated with the onset and progression of melanoma. In this review article, we report on current therapeutic options in melanoma treatment with a focus on distinct epigenetic alterations and how their reversal, by specific drug compounds, can restore a normal phenotype. In particular, we concentrate on how single and/or combinatorial therapeutic approaches have utilized epigenetic drug compounds in being effective against malignant melanoma. Finally, the role of deregulated epigenetic mechanisms in promoting drug resistance to targeted therapies and immune checkpoint inhibitors is presented leading to the development of newly synthesized and/or improved drug compounds ca-pable of targeting the epigenome of malignant melanoma.(c) 2022 Elsevier Inc. All rights reserved.

Automated summary

This review article discusses current therapeutic options in melanoma treatment, focusing on distinct epigenetic alterations and how specific drug compounds can reverse these changes. Abnormal epigenetic mechanisms have been found to be associated with the onset, progression, and drug resistance of melanoma.