BRAF V600

This study provides a regional molecular profile of advanced CRC in Bulgaria, highlighting a high prevalence of KRAS mutations and dMMR status, while underrepresentation of rare targetable alterations, likely due to limited use of broad molecular profiling. The association between stromal features and MMR status supports their potential role as surrogate markers in settings with constrained testing resources. Findings underscore the urgent need for equitable access to molecular diagnostics and targeted therapies to close the survival gap between Eastern and Western Europe.

Because these disorders may be limited to the skin or be a manifestation of a systemic histiocytic neoplasm, correlation with clinical features is essential. Molecular genetic analysis to identify mutations in the mitogen-activated protein kinase pathway should be considered to provide options for targeted therapy.

Although the FDA-approved combination of encorafenib and cetuximab provides clinical benefit in this population, only 22% of patients respond and most eventually develop resistance...Importantly, we demonstrate that addition of TVB3664 to the PLX8394 or encorafenib regimen significantly postpones development of resistance to BRAF-targeted therapy by inhibiting the cell cycle progression via a decrease in pRb (Ser780) and downregulation of E2F transcription factor and Cyclin D1 expression. Consistently, clinical data show that patients with BRAFV600E CRC who have high FASN expression in tumor tissues have higher expression of cell cycle-associated genes, including CDKs, E2F, CCDN1 (Cyclin D1), survivin, and MKI67. Collectively, these findings identify FASN-driven lipid metabolism as a critical mediator of resistance to BRAF-targeted therapy and suggest that incorporation of FASN inhibitors may enhance therapeutic efficacy and delay acquired resistance in BRAFV600E CRC.

Immunofluorescence revealed that pharmacologic inhibition of oncogenic MAPK signaling reduces DRP1-S616Ⓟ levels which correlates with mitochondrial hyperfusion; while immunohistochemistry showed that elevated DRP1-S616Ⓟ expression in human tissues correlates with BRAF V600E disease. Together, these findings establish 3G11 as a specific, versatile, renewable, and cost-effective tool for studying mitochondrial division, with strong potential for clinical applications.

The patient remains recurrence-free two years after surgery. This case highlights the potential for conversion surgery in stage IV BRAF-mutated colorectal cancer with NEC.

Testing asymptomatic relatives identified two first-degree relatives with MSH2 mutations. These findings underscore the critical need for CRC-adapted preventive oncology and support the implementation of a national LS screening program in Greece, aligned with international guidelines.

Uptake and impact of encorafenib plus cetuximab (EC), since being available in Australia from May 2019, were examined. The COALA study provides the first Australian real-world profile of BRAFV600E-mutated mCRC. These findings underscore the importance of early and effective therapeutic strategies, and identify a novel, disproportionately affected very-young subgroup requiring targeted research and clinical focus.

P1, N=14, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2028 --> Dec 2026

P1, N=16, Terminated, Rutgers, The State University of New Jersey | Active, not recruiting --> Terminated; accrual goal met

P2, N=18, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2026 --> Jan 2027

P3, N=480, Recruiting, University of Campania Luigi Vanvitelli

P2, N=93, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed | Phase classification: P1/2 --> P2