BRAF-Mutated Colorectal Cancer: Clinical and Molecular Insights.
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Bevacizumab
/ therapeutic use
Colorectal Neoplasms
/ drug therapy
Drug Resistance, Neoplasm
/ genetics
Female
Humans
MAP Kinase Signaling System
/ drug effects
Male
Melanoma
/ drug therapy
Mutation
Prognosis
Proto-Oncogene Proteins B-raf
/ antagonists & inhibitors
BRAF inhibitors
BRAF mutation
colorectal cancer
molecular targets
targeted therapy
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
28 Oct 2019
28 Oct 2019
Historique:
received:
15
10
2019
revised:
23
10
2019
accepted:
24
10
2019
entrez:
31
10
2019
pubmed:
31
10
2019
medline:
31
3
2020
Statut:
epublish
Résumé
Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world. It is a heterogeneous disease, which can be classified into different subtypes, characterized by specific molecular and morphological alterations. In this context, BRAF mutations are found in about 10% of CRC patients and define a particular subtype, characterized by a dismal prognosis, with a median survival of less than 12 months. Chemotherapy plus bevacizumab is the current standard therapy in first-line treatment of BRAF-mutated metastatic CRC (mCRC), with triplet (FOLFOXIRI) plus bevacizumab as a valid option in patients with a good performance status. BRAF inhibitors are not so effective as compared to melanoma, because of various resistance mechanisms. However, the recently published results of the BEACON trial will establish a new standard of care in this setting. This review provides insights into the molecular underpinnings underlying the resistance to standard treatment of BRAF-mutated CRCs, with a focus on their molecular heterogeneity and on the research perspectives both from a translational and a clinical point of view.
Identifiants
pubmed: 31661924
pii: ijms20215369
doi: 10.3390/ijms20215369
pmc: PMC6861966
pii:
doi:
Substances chimiques
Bevacizumab
2S9ZZM9Q9V
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors have no conflicts of interest to disclose.
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