KRAS as a druggable target in NSCLC: Rising like a phoenix after decades of development failures.
Antineoplastic Agents
/ therapeutic use
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Female
Forecasting
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Immunotherapy
/ methods
Lung Neoplasms
/ drug therapy
Male
Molecular Targeted Therapy
Mutation
Proto-Oncogene Proteins p21(ras)
/ drug effects
Survival Analysis
Treatment Outcome
Checkpoint inhibitors
KRAS
NSCLC
Journal
Cancer treatment reviews
ISSN: 1532-1967
Titre abrégé: Cancer Treat Rev
Pays: Netherlands
ID NLM: 7502030
Informations de publication
Date de publication:
Apr 2020
Apr 2020
Historique:
received:
18
11
2019
revised:
27
01
2020
accepted:
31
01
2020
pubmed:
18
2
2020
medline:
25
3
2020
entrez:
17
2
2020
Statut:
ppublish
Résumé
Cancers of nearly all lineages harbor alterations that deregulate mitogen-activated protein kinase signaling, a crucial signaling pathway for tumor formation and maintenance. Of these, KRAS mutations are the most frequent gain-of-function alterations found in patients with cancer. In particular they represents the most common molecular alteration detected in non-small cell lung cancer (NSCLC) accounting for up to 25% of all oncogenic mutations. They were identified decades ago and prior efforts to target these proteins have been unsuccessful. KRAS mutation profiles (i.e. frequency of specific codon substitutions) in smokers and never-smokers are distinct and not all KRAS alterations are driver mutations. KRAS has evolved from a mutation with possible predictive value to a therapeutic target with great promise. Here, we will discuss the biology of KRAS in lung cancer and its clinical implications in oncology today and in the foreseeable future.
Identifiants
pubmed: 32062493
pii: S0305-7372(20)30016-5
doi: 10.1016/j.ctrv.2020.101978
pmc: PMC7448574
mid: NIHMS1616218
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
KRAS protein, human
0
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
101978Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
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