BRAF (B-raf proto-oncogene)

The required post-marketing clinical trial (FIREFLY-2) was well underway at the time of accelerated approval. This represents the first FDA approval of a systemic therapy for the treatment of patients with pLGG with BRAF fusions or rearrangements.

P1/2, N=53, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2025 --> Jan 2026

In a resource-limited setting, where access to ICIs and targeted therapies is not feasible, and in patients who fail to tolerate these therapies, oral chemotherapy continues to remain effective and is worth trying in patients with poor PS.

P2, N=186, Recruiting, Alliance for Clinical Trials in Oncology | Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Oct 2025 --> Oct 2026

Less than 10% of patients (n = 20) had metastatic dMMR CRC. These patients could be considered candidates for immune checkpoint inhibitor therapy, a small number that would not significantly burden the NZ health system if funded. The vast majority of dMMR CRC was sporadic. Rates of testing could be improved.

P1/2, N=30, Recruiting, Cancer Hospital Chinese Academy of Medical Science, Shenzhen Center

This exploratory analysis from a randomized phase II study shows a non-significant improvement in TTR from the addition of neoadjuvant panitumumab to peri-operative FOLFOX in RAS/BRAF-wt LACC. Hyperselection with EREG/AREG status was associated with increased efficacy. A dedicated prospective trial within a biomarker selected population is under development.

P2, N=240, Active, not recruiting, SWOG Cancer Research Network | Trial completion date: Nov 2024 --> Nov 2025

A multivariate analysis revealed that postresection anti-EGFR mAb was an independent predictor of prolonged OS. In conclusion, for mCRC patients who have undergone secondary resection after first-line anti-EGFR mAb plus doublet chemotherapy, continuing anti-EGFR mAb may significantly extend OS, regardless of the primary tumor location.

This comprehensive review summarizes the recent modifications to the World Health Organization's categorization of AMs, explores progress in elucidating their underlying molecular pathways, and evaluates emerging targeted treatment modalities. Our objective is to present a thorough synthesis of contemporary scientific discoveries and therapeutic interventions, potentially paving the way for more efficacious and individualized clinical management protocols for this complex neoplasm.

P2, N=340, Recruiting, Replimune Inc. | Trial completion date: Jun 2025 --> Dec 2028 | Trial primary completion date: Jun 2025 --> Dec 2025

P1, N=15, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting --> Active, not recruiting

P1, N=91, Completed, Agenus Inc. | Active, not recruiting --> Completed | N=67 --> 91 | Trial completion date: Jun 2027 --> Nov 2024 | Trial primary completion date: Jun 2025 --> Feb 2024

The high prevalence of whole-genome duplication events in BRAF/NRAS-mutated tumors suggests a synergistic carcinogenic effect that warrants further investigation. In summary, our study provides important insights into the genetic underpinnings of acral melanoma in East Asians, creating opportunities for targeted therapies.

In MSS CRC, cluster 5 (APCAMER1-KRAS) and cluster 2 (RNF43-BRAF-PIK3CA) were predominant, and cluster 5 showed a superior overall survival compared with cluster 2. This extensive heterogeneity in driver gene mutations underscores the complexity of CRC and suggests significant implications for treatment and prognostic assessments.

Protein-protein interaction network analysis further indicated significant interconnectivity among the identified prognostic genes. Overall, these insights underscore critical immune interactions and potential therapeutic targets to combat melanoma resistance, paving the way for more personalized and effective treatment strategies.

EGFR and PIK3CA amplifications, detectable via ctDNA but missed in tissue biopsies, indicated emerging resistance mechanisms. The SHIZUKU-HN study demonstrates the potential of ctDNA as a dynamic biomarker in HNSCC, offering early insights into treatment efficacy and informing personalized ICI therapy.

An immunofluorescence study of tumor sections showed notable reductions in proliferation marker ki67 and the vasculogenesis marker CD31 in treated tumors. These findings promote LA as a potential nutraceutical lead for the control of the BRAF V600E mutant melanoma.

BRAFV600E tend to display florid nuclear features, whereas the RAS- mutation is associated with subtle nuclear features. These findings emphasize the distinct cytological profiles of BL and RL PTC, reinforcing the need for precise subtyping to guide tailored management.

Initial treatments, including carboplatin, etoposide, and taxane-based chemotherapy, were ineffective. After 76 cycles, she continues to tolerate therapy well with minimal adverse events. This case highlights the potential of targeted therapies such as copanlisib for treating METAM, providing a promising therapeutic option for patients with PIK3CA mutations.

© 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

Thus far, the management of stage III BRAF-mutant patients following neoadjuvant ICI, treatment de-escalation in long-term TT responders in the advanced setting and the management of symptomatic brain metastases remain areas of debate. Further work on predictive and prognostic biomarkers for patients with BRAF-mutant melanoma patients will assist in clinical decision making.

For example, cases had significantly higher levels of 25 chemical features compared to controls (p < 0.05). This is the largest study to date to quantify such a wide breadth of contaminant exposure levels associated with canine urothelial carcinoma and the first to assess a population with subclinical disease, highlighting pet dogs as models to study environmental contributions to cancer risk, advancing both human and veterinary health.

Our present study suggested that compared to patients with a normal BMI, overweight and obese patients had a greater risk of multifocality and bilaterality of PTC. No significant associations were observed between higher BMI and the more advanced tumor-node-metastasis stage or BRAFV600E mutational status.

These findings suggest the existence of a molecular phenomenon of "leap" between pathways, which we have termed "pathway leap." This could explain the enigmatic group of tumors that the WHO classifies under the heading of "combined nevi." This group could be more frequent than suspected, because microdissection is not a technique commonly used in the daily diagnosis of melanocytic tumors.

Integrating genetic, environmental, and immune factors, personalized therapies are pivotal for efficacy. Continued research is crucial for optimizing treatments and improving patient outcomes, emphasizing the need for multifaceted, patient-tailored approaches in CRC management.

Six-month PFS in both arms was consistent with that achieved with FU/bev, whilst the rate was numerically higher for Arm B. Baseline comprehensive geriatric assessments were feasible and OTU was high. Both treatment arms might be suitable in appropriately selected patients.

despite s-CPM being associated with impaired OS after CRS-HIPEC, the onset of PM was not found to be an independent determinant for survival. High-risk molecular and histological features strongly influence oncological outcomes after CRS-HIPEC. This is valuable data that could aid in preoperative patient selection process for CRS-HIPEC.

These data suggest that the neuronal dysfunction observed in the systemic CFC mouse model is due to the disruption of homeostasis of the RAS/MAPK signaling pathway by the activated Braf mutant after maturation, rather than abnormal development of the brain. A similar mechanism may be possible in human CFC syndrome.

Encorafenib plus cetuximab (EC) is the standard of care for pre-treated BRAF V600E mutated metastatic colorectal cancer (mCRC)...We aimed to assess potential predictors of primary resistance to EC ± binimetinib (B) and relationships of DpR/ETS with survival outcomes and clinical characteristics...DpR was also significantly associated with longer DoR (p DpR⩾30% = 0.04; p DpR⩾15% = 0.04; p cont. = 0.02), whereas no relationships of ETS with PFS, OS or DoR were detected. A DpR of at least 15% independently predicts PFS benefit in BRAF V600E mutated mCRC patients treated with second-line EC ± B.

P2, N=30, Recruiting, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | Trial completion date: Feb 2029 --> Feb 2030 | Trial primary completion date: Feb 2025 --> Feb 2030

P1/2, N=125, Active, not recruiting, Kahr Medical | Recruiting --> Active, not recruiting

P2, N=34, Completed, Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori | Active, not recruiting --> Completed | Trial completion date: Sep 2024 --> Jun 2024

P2, N=72, Completed, German Cancer Research Center | Active, not recruiting --> Completed | N=175 --> 72 | Trial completion date: Jun 2025 --> Dec 2024 | Trial primary completion date: Jun 2025 --> Dec 2024

P1, N=2, Active, not recruiting, Richard Wu | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=36, Not yet recruiting, Fudan University

P2, N=2316, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2027 --> Jun 2025 | Trial primary completion date: Sep 2027 --> Jun 2025

P2, N=20, Recruiting, Melanoma Institute Australia | Trial completion date: Dec 2034 --> Dec 2035 | Trial primary completion date: Dec 2024 --> Dec 2025

P1/2, N=257, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | N=384 --> 257 | Trial completion date: Dec 2025 --> Dec 2026

P2, N=218, Recruiting, Melanoma Institute Australia | Trial completion date: Aug 2025 --> Aug 2029 | Trial primary completion date: Aug 2024 --> Aug 2026

P1/2, N=197, Recruiting, BioInvent International AB | N=90 --> 197 | Trial completion date: Jan 2026 --> Nov 2027 | Trial primary completion date: Nov 2025 --> Nov 2027

P3, N=677, Completed, Shanghai Henlius Biotech | Active, not recruiting --> Completed