Drugging the Epigenome: Overcoming Resistance to Targeted and Immunotherapies in Melanoma.
JID Innov
; 2(2): 100090, 2022 Mar.
Article
en En
| MEDLINE
| ID: mdl-35199090
This past decade has seen tremendous advances in understanding the molecular pathogenesis of melanoma and the development of novel effective therapies for melanoma. Targeted therapies and immunotherapies that extend survival of patients with advanced disease have been developed; however, the vast majority of patients experience relapse and therapeutic resistance over time. Moreover, cellular plasticity has been demonstrated to be a driver of therapeutic resistance mechanisms in melanoma and other cancers, largely functioning through epigenetic mechanisms, suggesting that targeting of the cancer epigenetic landscape may prove a worthwhile endeavor to ensure durable treatment responses and cures. Here, we review the epigenetic alterations that characterize melanoma development, progression, and resistance to targeted therapies as well as epigenetic therapies currently in use and under development for melanoma and other cancers. We further assess the landscape of epigenetic therapies in clinical trials for melanoma and provide a framework for future advances in epigenetic therapies to circumvent the development of therapeutic resistance in melanoma.
BRAFi, BRAF inhibitor; DNMT, DNA methyltransferase; DNMTi, DNA methyltransferase inhibitor; EZH2, enhancer of zeste homolog 2; EZH2i, enhancer of zeste homolog 2 inhibitor; HAT, histone acetyltransferase; HDAC, histone deacetylase; HDACi, histone deacetylase inhibitor; MEKi, MAPK/extracellular signalâregulated kinase inhibitor; PTM, post-translational modification; SIRT, sirtuin; TMZ, temozolomide; dsRNA, double-stranded RNA
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
JID Innov
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos