Article (Scientific journals)
NRAS mutant melanoma: Towards better therapies
RANDIC, Tijana; KOZAR, Ines; MARGUE, Christiane et al.
2021In Cancer Treatment Reviews, 99
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Keywords :
cutaneous melanoma; NRAS mutation; MEKi/CDK4/6i dual therapy; Resistance mechanisms; New combination therapies
Abstract :
[en] Genetic alterations affecting RAS proteins are commonly found in human cancers. Roughly a fourth of melanoma patients carry activating NRAS mutations, rendering this malignancy particularly challenging to treat. Although the development of targeted as well as immunotherapies led to a substantial improvement in the overall survival of non-NRASmut melanoma patients (e.g. BRAFmut), patients with NRASmut melanomas have an overall poorer prognosis due to the high aggressiveness of RASmut tumors, lack of efficient targeted therapies or rapidly emerging resistance to existing treatments. Understanding how NRAS-driven melanomas develop therapy resistance by maintaining cell cycle progression and survival is crucial to develop more effective and specific treatments for this group of melanoma patients. In this review, we provide an updated summary of currently available therapeutic options for NRASmut melanoma patients with a focus on combined inhibition of MAPK signaling and CDK4/6-driven cell cycle progression and mechanisms of the inevitably developing resistance to these treatments. We conclude with an outlook on the most promising novel therapeutic approaches for melanoma patients with constitutively active NRAS.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
RANDIC, Tijana ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
KOZAR, Ines ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
MARGUE, Christiane  ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
Utikal, Jochen;  Skin Cancer Unit, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany
KREIS, Stephanie ;  University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
External co-authors :
yes
Language :
English
Title :
NRAS mutant melanoma: Towards better therapies
Publication date :
29 May 2021
Journal title :
Cancer Treatment Reviews
ISSN :
1532-1967
Publisher :
W. B. Saunders Co., London, United Kingdom
Volume :
99
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
FNR - Fonds National de la Recherche [LU]
Available on ORBilu :
since 08 July 2021

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