BRAF (B-raf proto-oncogene)

BRAFV600E and TERT promoter co-mutation, identifiable preoperatively, defines a distinct PTC subtype with a profoundly aggressive clinicopathological profile and a significantly elevated risk of recurrence. This combined molecular signature is a potent preoperative biomarker for stratifying patients into the highest-risk category, potentially guiding more individualized initial therapeutic strategies.

The review addresses rationale testing for BRAF alterations, selection, and monitoring of targeted therapies, management of treatment-related toxicities, approaches to resistance, and priorities for future research. It aims to provide practical, evidence-based guidance for clinicians while highlighting gaps to inform prospective studies.

BRAF mutation is presumed to be associated with tumor progression and may predict growth of PTMC. Genetic testing including BRAF testing may help distinguishing rapid-growing thyroid cancer.

These findings may represent a previously undescribed type of salivary gland tumor. However, additional reports of similar lesions are necessary for definitive characterization.

Raising physician awareness, as reflected by the untested rate, is a crucial factor in conducting clinical trials to implement perioperative cancer genomic medicine.

P1/2, N=67, Recruiting, D3 Bio (Wuxi) Co., Ltd | Active, not recruiting --> Recruiting | Trial completion date: Apr 2028 --> Aug 2028 | Trial primary completion date: Apr 2028 --> Aug 2028

P1, N=83, Active, not recruiting, HiFiBiO Therapeutics | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

However, interpretation of these findings is limited by the non-randomized design and differences in rituximab exposure between groups, which may have contributed to the observed outcomes and limited definitive conclusions. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.

Reduced-dose dabrafenib and trametinib were initiated with prophylactic naproxen to mitigate the risk of pyrexia. Treatment has been continued for over 6 months with sustained disease stability. This case suggests that an upfront dose-attenuation strategy combined with proactive toxicity management, including pyrexia prophylaxis, may represent a practical approach to maintain treatment continuity and clinical benefit in selected very elderly or frail patients.

Molecular docking studies were performed on representative active compounds to rationalize observed biological activity and characterize key interactions within the ATP-binding sites of EGFR and B-RAF kinases. Collectively, these findings identify khellin-derived benzofuran-pyrazoline hybrid systems as promising candidates for targeting kinases and as potential anticancer agents, providing a rational basis for further structural optimization and mechanistic investigation.

PD-L1 is a robust biomarker of aggressiveness in PTC. Integrating PD-L1 testing with molecular profiling can enhance postoperative risk stratification and guide personalized management.

Overall survival analysis showed no consistent prognostic disadvantage for CO, except in EGFR-KRAS co-mutant NSCLC. These findings further refine the ME landscape of BRAF, KRAS, and EGFR variants, offering a variant-level reference to support mutation-informed precision oncology.