Resistance to BRAF-targeted therapy in melanoma

BRAF mutations are identified in 40–50% of patients with melanoma. Treatment of these patients with either of two BRAF inhibitors (vemurafenib, dabrafenib) or the MEK inhibitor trametinib is associated with improved clinical benefit (response rate, progression free survival, and overall survival) co...

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Vydáno v:European journal of cancer (1990) Ročník 49; číslo 6; s. 1297 - 1304
Hlavní autoři: Sullivan, Ryan J., Flaherty, Keith T.
Médium: Journal Article
Jazyk:angličtina
Vydáno: Kidlington Elsevier Ltd 01.04.2013
Elsevier
Témata:
Biological and medical sciences
BRAF inhibitor resistance
Disease-Free Survival
Drug Resistance, Neoplasm - genetics
Hematology, Oncology and Palliative Medicine
Humans
Imidazoles - therapeutic use
Indoles - therapeutic use
MAP Kinase Signaling System - drug effects
Medical sciences
Melanoma
Melanoma - drug therapy
Melanoma - genetics
Molecular targeted therapy
Multiple tumors. Solid tumors. Tumors in childhood (general aspects)
Mutation
Oximes - therapeutic use
Pharmacology. Drug treatments
Protein Kinase Inhibitors - therapeutic use
Proto-Oncogene Proteins B-raf - antagonists & inhibitors
Proto-Oncogene Proteins B-raf - genetics
Pyridones - therapeutic use
Pyrimidinones - therapeutic use
Sulfonamides - therapeutic use
Tumors
Molecular targeted therapy
BRAF inhibitor resistance
Melanoma
Targeted therapy
Malignant tumor
Resistance
BRAF Gene
Cancerology
Treatment
C-Onc gene
Targeted drug
Malignant melanoma
Inhibitor
Protooncogene
Cancer
ISSN:0959-8049, 1879-0852, 1879-0852
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Popis
Shrnutí:BRAF mutations are identified in 40–50% of patients with melanoma. Treatment of these patients with either of two BRAF inhibitors (vemurafenib, dabrafenib) or the MEK inhibitor trametinib is associated with improved clinical benefit (response rate, progression free survival, and overall survival) compared with treatment with chemotherapy in three phase III trials. Unfortunately, most patients, including those who experience initial, profound tumour regression, have evidence of disease progression within 6–8months after commencing therapy with one of these agents. The mechanisms of resistance are varied and include activation of alternative signalling pathways as well as reactivating the MAP kinase pathway through alternative means. This review describes relevant aspects of MAP kinase pathway signalling, summarises the clinical data with BRAF and MEK inhibitors, presents the known resistance mechanisms to BRAF inhibitor therapy, and provides some strategies for how resistance may be overcome.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
ObjectType-Review-3
content type line 23
ISSN:0959-8049
1879-0852
1879-0852
DOI:10.1016/j.ejca.2012.11.019