Encorafenib, cetuximab, and binimetinib are targeted therapies developed for metastatic colorectal cancer with a BRAF V600E mutation. The case highlights the potential use of BRAF V600E targeted therapy in BRAF V600E-mutated duodenal cancer and the importance of molecular profiling in rare cancers. Further research is needed on the effect and safety of targeted therapy for small bowel adenocarcinoma.

ABM-1310 showed a favorable safety profile and encouraging intracranial activity. These findings support continued evaluation for CNS tumors and in cancer patients with prior BRAF inhibitor exposure.

Using a panel of BRAFV600E positive YUMM lines, we find that, following chronic vemurafenib treatment, SOX10 is lost whereas SOX9 is induced...Overall, our data show that the loss of SOX10 and SOX9 induction are critical to program drug resistance. Furthermore, we show that the YUMM cell lines represent a good murine model to investigate transitions to an acquired drug resistant state.

Interestingly, these so-called NaJa lines displayed distinct differentiation states and responses to the clinically relevant RAF inhibitors (RAFi) encorafenib and exarafenib, thereby resembling the clinical heterogeneity of BRAFV600E-driven CRC. RAFi resistance was overcome by the EGFR-family inhibitor afatinib...Upon re-transplantation into syngeneic mice, all NaJa lines established aggressive tumors with distinct tumor microenvironments matching to their differentiation states. Thus, the NaJa lines provide a unique tool to study tumor heterogeneity, drug resistance and the interplay between tumor, stroma and immune cells in BRAFV600E-driven CRC.

Glioblastoma (GBM) is the most lethal brain tumor, characterized by strong resistance to conventional therapies. Furthermore, vemurafenib, which targets FOSL1, was identified as a potential therapeutic agent against TMZ-resistant GBM in a mouse model. These findings suggest that FOSL1 promotes TMZ chemoresistance by regulating IL-6-pSTAT3Tyr705-mediated stemness in GBM cells, making it a promising therapeutic target to overcome chemoresistance in GBM.

The greatest benefits of encorafenib plus binimetinib were observed in patients with evidence of high TMB and/or tumor immune infiltration, suggesting potential immune contributions to efficacy, which were not observed with vemurafenib. BRAF V600 detectability in ctDNA appears to have utility as a marker of prognosis and response in this population.

These three compounds were also tested on the vemurafenib-resistant (A375R) and normal (HaCaT and MRC-5) cell lines, and compound 8 showed better cytotoxicity (IC50 = 8.84 ± 1.24 µM) and selectivity (>3.50) when compared to telmisartan (IC50 = 29.23 ± 3.88, selectivity > 2.40). All three compounds induced cell cycle arrest and disrupted mitochondrial morphology and membrane potential. These findings highlight their potential as non-antihypertensive telmisartan derivatives for melanoma therapy.

Data from this study provides provocative evidence that, while BRAF+/-MEK inhibitor therapy produces an increase in overall and clonal T cell infiltrates, there is limited evidence for generation of new or persistent tumor immunity. Thus, BRAFi/MEKi therapy may enable tumor-reactive T cells to infiltrate tumors but tumor control does not appear to depend on priming new immune responses.

P2, N=63, Active, not recruiting, Pierre Fabre Medicament | Trial completion date: Sep 2026 --> Dec 2026

P2, N=16, Active, not recruiting, Gruppo Oncologico del Nord-Ovest | Recruiting --> Active, not recruiting

In conclusion, our case highlights that the primary diagnostic clue for ECD may be a single yellowish plaque, which requires further investigation in relation to other systemic symptoms. Vemurafenib treatment may lead to regression of systemic symptoms and cutaneous yellowish plaques associated with ECD carrying a BRAF mutation.