BRAF (B-raf proto-oncogene)

P2, N=583, Recruiting, Chinese PLA General Hospital

P=N/A, N=131, Completed, First Affiliated Hospital of Chongqing Medical University

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.

These findings support the use of anti-EGFR rechallenge strategy aslater-line treatment when tumor shrinkage is a clinical priority. Further evidence from prospective trials is required.

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.

P2, N=70, Not yet recruiting, AHS Cancer Control Alberta | Trial completion date: Jan 2030 --> Jan 2031 | Trial primary completion date: Dec 2026 --> Dec 2027

This study provides a comprehensive genomic overview of AM, highlighting recurrent alterations in the MAPK and cell cycle pathways, and potential demographic-specific molecular signatures. These findings support the need for expanded molecular profiling to improve prognostic accuracy and identify targets for future therapy.

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.

Furthermore, pan-cancer analyses implicate the BRAF25 signature in poor prognosis across diverse BRAF-driven malignancies. In conclusion, stratifying patients by transcriptional BRAF oncogenic activity, instead of relying solely on BRAF mutation status, provides a more precise approach to guide clinical decision-making and improve therapeutic outcomes.

Between mCRC diagnosis and death or withdrawal, patients were frequently exposed to fluoropyrimidine (99.0%), irinotecan (96.2%), oxaliplatin (88.4%), anti-vascular endothelial growth factor (78.7%) and anti-epidermal growth factor receptor (40.1%). PROMETCO provided information on real-world prescribing patterns and efficacy. OS from mCRC diagnosis and PFS from 3L and beyond were similar to previous long-term follow-up data from clinical trials.

Persons who have a more pro-inflammatory lifestyle may have an increased recurrence risk (IRR 1.21, 95% CI 0.97-1.52), which was most pronounced for persons with MSS and KRAS or PIK3CA wildtype tumours (IRR 1.31, 95% CI 0.90-1.90 and IRR 1.30, 95% CI 0.98-1.71, respectively). Our results suggest that associations between the LIS and recurrence might differ based on molecular tumour characteristics.

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.