The "ART" of Epigenetics in Melanoma: From histone "Alterations, to Resistance and Therapies".
Animals
Chromatin Assembly and Disassembly
/ genetics
Cytotoxicity, Immunologic
Drug Resistance, Neoplasm
/ genetics
Epigenomics
/ methods
Histones
/ metabolism
Humans
Immunotherapy
/ adverse effects
Melanoma
/ drug therapy
Mice
Molecular Targeted Therapy
/ methods
Prognosis
Proto-Oncogene Proteins B-raf
/ metabolism
Skin Neoplasms
/ drug therapy
Uveal Neoplasms
/ genetics
Melanoma, Cutaneous Malignant
drug resistance
epigenetics
immunotherapy
melanoma
targeted therapy
Journal
Theranostics
ISSN: 1838-7640
Titre abrégé: Theranostics
Pays: Australia
ID NLM: 101552395
Informations de publication
Date de publication:
2020
2020
Historique:
received:
30
04
2019
accepted:
14
11
2019
entrez:
12
2
2020
pubmed:
12
2
2020
medline:
14
4
2021
Statut:
epublish
Résumé
Malignant melanoma is the most deadly form of skin cancer. It originates from melanocytic cells and can also arise at other body sites. Early diagnosis and appropriate medical care offer excellent prognosis with up to 5-year survival rate in more than 95% of all patients. However, long-term survival rate for metastatic melanoma patients remains at only 5%. Indeed, malignant melanoma is known for its notorious resistance to most current therapies and is characterized by both genetic and epigenetic alterations. In cutaneous melanoma (CM), genetic alterations have been implicated in drug resistance, yet the main cause of this resistance seems to be non-genetic in nature with a change in transcription programs within cell subpopulations. This change can adapt and escape targeted therapy and immunotherapy cytotoxic effects favoring relapse. Because they are reversible in nature, epigenetic changes are a growing focus in cancer research aiming to prevent or revert the drug resistance with current therapies. As such, the field of epigenetic therapeutics is among the most active area of preclinical and clinical research with effects of many classes of epigenetic drugs being investigated. Here, we review the multiplicity of epigenetic alterations, mainly histone alterations and chromatin remodeling in both cutaneous and uveal melanomas, opening opportunities for further research in the field and providing clues to specifically control these modifications. We also discuss how epigenetic dysregulations may be exploited to achieve clinical benefits for the patients, the limitations of these therapies, and recent data exploring this potential through combinatorial epigenetic and traditional therapeutic approaches.
Identifiants
pubmed: 32042336
doi: 10.7150/thno.36218
pii: thnov10p1777
pmc: PMC6993228
doi:
Substances chimiques
Histones
0
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1777-1797Informations de copyright
© The author(s).
Déclaration de conflit d'intérêts
Competing Interests: The authors have declared that no competing interest exists.
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