BRAF Alterations as Therapeutic Targets in Non-Small-Cell Lung Cancer.

Details

Serval ID
serval:BIB_110A91BCCD8A
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
BRAF Alterations as Therapeutic Targets in Non-Small-Cell Lung Cancer.
Journal
Journal of Thoracic Oncology : Official Publication of the International Association For the Study of Lung Cancer
Author(s)
Nguyen-Ngoc T., Bouchaab H., Adjei A.A., Peters S.
ISSN
1556-1380 (Electronic)
ISSN-L
1556-0864
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
10
Number
10
Pages
1396-1403
Language
english
Notes
Publication types: Journal Article ; Review
Publication Status: ppublish
Abstract
BACKGROUND: Several subsets of non-small-cell lung cancer (NSCLC) are defined by molecular alterations acting as tumor drivers, some of them being currently therapeutically actionable. The rat sarcoma (RAS)-rapidly accelerated fibrosarcoma (RAF)-mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway constitutes an attractive potential target, as v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutations occur in 2-4% of NSCLC adenocarcinoma.
METHODS: Here, we review the latest clinical data on BRAF serine/threonine kinase inhibitors in NSCLC.
RESULTS: Treatment of V600E BRAF-mutated NSCLC with BRAF inhibitor monotherapy demonstrated encouraging antitumor activity. Combination of BRAF and MEK inhibitors using dabrafenib and trametinib is under evaluation. Preliminary data suggest superior efficacy compared with BRAF inhibitor monotherapy.
CONCLUSION: Targeting BRAF alterations represents a promising new therapeutic approach for a restricted subset of oncogene-addicted NSCLC. Prospect ive trials refining this strategy are ongoing. A next step will probably aim at combining BRAF inhibitors and immunotherapy or alternatively improve a multilevel mitogen-activated protein kinase (MAPK) pathway blockade by combining with ERK inhibitors.
Keywords
Animals, Carcinoma, Non-Small-Cell Lung/drug therapy, Carcinoma, Non-Small-Cell Lung/enzymology, Humans, Lung Neoplasms/drug therapy, Lung Neoplasms/enzymology, Molecular Targeted Therapy, Mutation, Proto-Oncogene Proteins B-raf/antagonists & inhibitors, Proto-Oncogene Proteins B-raf/genetics
Pubmed
Web of science
Open Access
Yes
Create date
19/10/2015 13:41
Last modification date
20/08/2019 13:38
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