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

Autor: Anestopoulos I; Department of Cancer Genetics, Therapeutics & Ultrastructural Pathology, The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus., Kyriakou S; Department of Cancer Genetics, Therapeutics & Ultrastructural Pathology, The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus., Tragkola V; Department of Cancer Genetics, Therapeutics & Ultrastructural Pathology, The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus., Paraskevaidis I; Department of Cancer Genetics, Therapeutics & Ultrastructural Pathology, The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus., Tzika E; Department of Cancer Genetics, Therapeutics & Ultrastructural Pathology, The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus., Mitsiogianni M; Medpace UK Ltd, London, UK., Deligiorgi MV; Laboratory of Pharmacology, Medical School, National & Kapodistrian University of Athens, Athens, Greece., Petrakis G; Saint George Hospital, Chania, Crete, Greece., Trafalis DT; Laboratory of Pharmacology, Medical School, National & Kapodistrian University of Athens, Athens, Greece., Botaitis S; Department of Surgery, Alexandroupolis University Hospital, Democritus University of Thrace School of Medicine, Alexandroupolis, Greece., Giatromanolaki A; Department of Pathology, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece., Koukourakis MI; Radiotherapy / Oncology, Radiobiology & Radiopathology Unit, Department of Medicine, School of Health Sciences, Democritus University of Thrace, Alexandroupolis, Greece., Franco R; Redox Biology Centre, University of Nebraska-Lincoln, Lincoln, NE, USA; School of Veterinary Medicine & Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA., Pappa A; Department of Molecular Biology & Genetics, Democritus University of Thrace, Alexandroupolis, Greece., Panayiotidis MI; Department of Cancer Genetics, Therapeutics & Ultrastructural Pathology, The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus. Electronic address: mihalisp@cing.ac.cy.
Jazyk: angličtina
Zdroj: Pharmacology & therapeutics [Pharmacol Ther] 2022 Dec; Vol. 240, pp. 108301. Date of Electronic Publication: 2022 Oct 23.
DOI: 10.1016/j.pharmthera.2022.108301
Abstrakt: Malignant melanoma is the most lethal type of skin cancer with high rates of mortality. Although current treatment 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 landscape, (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 capable of targeting the epigenome of malignant melanoma.
Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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