BRAF (B-raf proto-oncogene)

P1, N=75, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting | Trial completion date: Dec 2025 --> Jun 2027 | Trial primary completion date: Dec 2025 --> Jun 2027

P2, N=920, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

P1, N=17, Completed, H. Lee Moffitt Cancer Center and Research Institute | Active, not recruiting --> Completed

While dabrafenib and trametinib were well tolerated, treatment feasibility was restricted. These findings emphasize the urgent need for more robust research to identify effective therapeutic strategies for this molecular subgroup.

HG-PFP treatment inhibited NF1 mutant PDOs growth by reducing cells viability and impaired organoids formation and growth in NRAS mutant samples, while showing no effects in BRAF mutant samples. Taking together these findings provide a preclinical perspective on therapeutic potential of HG-PFP across different melanoma subtypes.

Targeted inhibition with the oral BRAF inhibitor encorafenib, combined with intravenous cetuximab targeting epithelial growth factor receptor (EGFR) and standard chemotherapy FOLFOX, has improved outcomes and received FDA approval in 2025 based on results from the phase III BREAKWATER trial...This case demonstrates that rectal and nasogastric administration of encorafenib is feasible, achieves therapeutic plasma concentrations, and induces objective and clinical remission in context of FOLFOX+EC. Short-term safety appeared manageable, though increased infection risk cannot be excluded.

P4, N=90, Not yet recruiting, NYU Langone Health

P=N/A, N=396, Recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University | Not yet recruiting --> Recruiting

TP53 mutations appear to be an independent prognostic marker for prolonged progression-free survival in patients with metastatic colorectal cancer. Although the difference in overall survival was not statistically significant, these findings warrant further validation in prospective studies to confirm the prognostic utility of TP53 in therapeutic stratification.

This paper systematically reviews the mechanisms underlying therapy-induced metabolic reprogramming in BRAF-mutant melanoma and explores potential combinatorial strategies that target these metabolic vulnerabilities alongside established melanoma therapies. Key metabolic targets with promising therapeutic potential identified include lysine-specific demethylase 1, oxidative phosphorylation components, phosphoglycerate dehydrogenase, indoleamine 2,3-dioxygenase 1 and lipid metabolism enzymes such as fatty acid synthase and 3-hydroxy-3-methylglutaryl-coenzyme a reductase.

Genetic loss of KLF4 or AXL depletion reduced melanoma cell migration and invasion, suggesting a key role of KLF4 in the regulation of invasiveness. Our study describes a novel ERK5/KLF4/AXL signaling axis that drives MEKi resistance and metastatic potential in NRAS-mutant melanoma and highlights this axis as a potential target to improve MAPK-directed and potentially immune therapies.