Targeting BRAF and RAS in Colorectal Cancer.
Helene BellioJean David FumetFrançois GhiringhelliPublished in: Cancers (2021)
Colorectal cancer (CRC) is still one of the most frequent forms of cancer in the world in terms of incidence. Around 40% of CRC patients carry a mutation of the Kirsten rat sarcoma (KRAS) gene, while 10% have a mutation in the B-Raf proto-oncogene serine/threonine kinase (BRAF) gene. These mutations are responsible for dysregulation of the mitogen-associated protein kinase (MAPK) pathway, leading to the proliferation, differentiation, angiogenesis, and resistance to apoptosis of cells. Activation of the MAPK pathway results in adaptive therapeutic resistance, rendering EGFR inhibitors ineffective. This review aims to highlight the recent findings that have improved our understanding of KRAS and BRAF mutations in colorectal cancer and to describe new targeted therapies, used alone or in combination.
Keyphrases
- protein kinase
- wild type
- signaling pathway
- oxidative stress
- cell cycle arrest
- induced apoptosis
- pi k akt
- end stage renal disease
- small cell lung cancer
- ejection fraction
- chronic kidney disease
- cell death
- copy number
- endoplasmic reticulum stress
- tyrosine kinase
- genome wide
- endothelial cells
- peritoneal dialysis
- prognostic factors
- genome wide identification
- immune response
- vascular endothelial growth factor
- cell proliferation
- inflammatory response