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Improvements in Clinical Outcomes for BRAF V600E -Mutant Metastatic Colorectal Cancer.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2020 Sep 01; Vol. 26 (17), pp. 4435-4441. Date of Electronic Publication: 2020 Apr 06. - Publication Year :
- 2020
-
Abstract
- Although the last two decades have seen a broad improvement in overall survival, colorectal cancer is still the second leading cause of cancer deaths worldwide. Patient populations continue to face poor disease prognoses due to the challenges of early detection and the molecular subtypes driving their colorectal cancer. Consequently, many patients present with metastatic colorectal cancer, which often limits options and shifts treatment focus away from curative interventions. BRAF <superscript>V600E</superscript> mutations are present in approximately 10% of colorectal cancer tumors and are associated with uninhibited cell proliferation, reduced apoptosis, and resistance to standard therapeutic options. In colorectal cancer, BRAF <superscript>V600E</superscript> mutations are associated with decreased overall survival, poor treatment responses, and different patterns of metastatic spread compared with tumors with wild-type BRAF Success in treating other BRAF <superscript>V600E</superscript> -mutant cancers with BRAF inhibitors as monotherapy has not translated into efficacious treatment of metastatic colorectal cancer. Consequently, combination therapy with inhibitors of BRAF, MEK, and EGFR, which overcomes the innate treatment-resistant characteristics of BRAF <superscript>V600E</superscript> -mutant colorectal cancer, is now recommended by treatment guidelines.<br /> (©2020 American Association for Cancer Research.)
- Subjects :
- Antineoplastic Combined Chemotherapy Protocols pharmacology
Colorectal Neoplasms genetics
Colorectal Neoplasms mortality
Colorectal Neoplasms pathology
Drug Resistance, Neoplasm drug effects
Drug Resistance, Neoplasm genetics
ErbB Receptors antagonists & inhibitors
Humans
Mitogen-Activated Protein Kinase Kinases antagonists & inhibitors
Mutation
Progression-Free Survival
Proto-Oncogene Proteins B-raf antagonists & inhibitors
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Colorectal Neoplasms drug therapy
Protein Kinase Inhibitors therapeutic use
Proto-Oncogene Proteins B-raf genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 26
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 32253230
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-19-3809