The Evolutionary Landscape of Treatment for BRAFV600E Mutant Metastatic Colorectal Cancer.
Gianluca MauriErica BonazzinaAlessio AmatuFederica TosiKatia BencardinoViviana GoriDaniela MassihniaTiziana CipaniFrancesco SpinaSilvia GhezziSalvatore SienaAndrea Sartore-BianchiPublished in: Cancers (2021)
The BRAFV600E mutation is found in 8-10% of metastatic colorectal cancer (mCRC) patients and it is recognized as a poor prognostic factor with a median overall survival inferior to 20 months. At present, besides immune checkpoint inhibitors (CPIs) for those tumors with concomitant MSI-H status, recommended treatment options include cytotoxic chemotherapy + anti-VEGF in the first line setting, and a combination of EGFR and a BRAF inhibitor (cetuximab plus encorafenib) in second line. However, even with the latter targeted approach, acquired resistance limits the possibility of more than an incremental benefit and survival is still dismal. In this review, we discuss current treatment options for this subset of patients and perform a systematic review of ongoing clinical trials. Overall, we identified six emerging strategies: targeting MAPK pathway (monotherapy or combinations), targeting MAPK pathway combined with cytotoxic agents, intensive cytotoxic regimen combinations, targeted agents combined with CPIs, oxidative stress induction, and cytotoxic agents combined with antiangiogenic drugs and CPIs. In the future, the integration of new therapeutic strategies targeting key players in the BRAFV600E oncogenic pathways with current treatment approach based on cytotoxic chemotherapy and surgery is likely to redefine the treatment landscape of these CRC patients.
Keyphrases
- prognostic factors
- metastatic colorectal cancer
- end stage renal disease
- oxidative stress
- ejection fraction
- clinical trial
- newly diagnosed
- cancer therapy
- small cell lung cancer
- chronic kidney disease
- randomized controlled trial
- signaling pathway
- peritoneal dialysis
- minimally invasive
- gene expression
- squamous cell carcinoma
- cell proliferation
- dna methylation
- patient reported outcomes
- dna damage
- endothelial cells
- ischemia reperfusion injury
- free survival
- radiation therapy
- open label
- rectal cancer
- smoking cessation
- heat shock protein
- phase ii