RAS pathway regulation in melanoma.
Cancer genetics
Melanoma
RAS pathway
Signaling
Targeted therapies
Journal
Disease models & mechanisms
ISSN: 1754-8411
Titre abrégé: Dis Model Mech
Pays: England
ID NLM: 101483332
Informations de publication
Date de publication:
01 02 2022
01 02 2022
Historique:
entrez:
2
3
2022
pubmed:
3
3
2022
medline:
3
5
2022
Statut:
ppublish
Résumé
Activating mutations in RAS genes are the most common genetic driver of human cancers. Yet, drugging this small GTPase has proven extremely challenging and therapeutic strategies targeting these recurrent alterations have long had limited success. To circumvent this difficulty, research has focused on the molecular dissection of the RAS pathway to gain a more-precise mechanistic understanding of its regulation, with the hope to identify new pharmacological approaches. Here, we review the current knowledge on the (dys)regulation of the RAS pathway, using melanoma as a paradigm. We first present a map of the main proteins involved in the RAS pathway, highlighting recent insights into their molecular roles and diverse mechanisms of regulation. We then overview genetic data pertaining to RAS pathway alterations in melanoma, along with insight into other cancers, that inform the biological function of members of the pathway. Finally, we describe the clinical implications of RAS pathway dysregulation in melanoma, discuss past and current approaches aimed at drugging the RAS pathway, and outline future opportunities for therapeutic development.
Identifiants
pubmed: 35234863
pii: 274596
doi: 10.1242/dmm.049229
pmc: PMC8905719
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
ras Proteins
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
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