MEK inhibitors for the treatment of NRAS mutant melanoma

Drug Design, Development and Therapy
Saro Sarkisian, Diwakar Davar

Abstract

Melanoma is increasing rapidly in incidence and prevalence, especially in younger females and older males. Treatment options have expanded beyond high-dose interleukin 2 and adoptive T-cell therapy to include inhibitors of immune checkpoints programmed death 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and small molecular inhibitors of pathways activated in melanoma, in particular the mitogen-activated protein kinase (MAPK) pathway. PD-1/CTLA-4 inhibitors and inhibitors of MAPK such as BRAF/MEK inhibitors have significantly improved survival in both the metastatic and, more recently, adjuvant settings. In this review, we discuss the preclinical data, clinical development, and potential use of novel MEK inhibitor binemetinib, particularly in the setting of NRAS mutant melanoma.

Citations

May 21, 2020·International Journal of Molecular Sciences·Kevin YangAndrzej T Slominski
Sep 5, 2020·The Oncologist·Alexandra Valeska MatterSimone M Goldinger
Aug 21, 2020·British Journal of Pharmacology·Imke A K BurmesterRalf J Ludwig
Apr 2, 2020·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Rahul SethPauline Funchain
Apr 3, 2019·International Journal of Molecular Sciences·Paola SavoiaOttavio Cremona
Apr 4, 2021·Cancers·Meet PatelNeelu Puri
May 1, 2021·International Journal of Molecular Sciences·Fabio ValentiAntonino Guerrisi
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Jul 3, 2021·Cancers·Rossella PuglisiGianfranco Mattia

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Methods Mentioned

BETA
GTPase
xenograft

Clinical Trials Mentioned

NCT01940809
NCT03374254
NCT03182673
NCT02586987
NCT03004105
NCT02967692
NCT03340558
NCT02908672
NCT03271047
NCT03170206

Software Mentioned

Array
coBRIM
COMBI

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