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.

CDK4/6 and SHP2 emerge as mediators of intrinsic resistance to BRAF/MEK inhibition in Class 2 & 3 BRAF mutant tumors. Therapeutic strategies combining CDK4/6 or SHP2 inhibitors with BRAF/MEK inhibitors in preclinical models show greater efficacy than BRAF/MEK inhibitors alone in these cancers.

A 48-year-old man with stage IV cutaneousmelanoma with BRAF V600E mutation achieved complete systemic remission with vemurafenib...Sub-Tenon's triamcinolone and intravenous immunoglobulin failed toimprove symptoms, but bilateral intravitreal dexamethasone implants (Ozurdex) resolved visual disturbances and normalized ERG...The absence of autoantibodies and late flares challenges current diagnostic paradigms, emphasizing ERG's critical role. Proactive ophthalmologic surveillance and individualized local therapy canpreserve vision in this underrecognized condition.

No new IRRs nor toxic deaths were reported. ENCO-PANI appears to be as safe and effective in pts treated for a BRAFm mCRC unable to continue CET and may represent a valid alternative therapeutic option in this setting.

Oral melanocytic neoplasms are rare and have distinct clinicopathological features. Despite this, a gap exists in molecular data regarding ODN and AMP. Conversely, OMN and OMM have distinct profiles; in particular, the latter may benefit modestly from tyrosine kinase inhibitor treatment, as KIT and BRAF mutations are sensitive to imatinib and vemurafenib, respectively.

Although vemurafenib showed efficacy in metastatic melanoma, off-label use resulted in limited benefit and increased adverse events. Unclear endpoints and underreported adverse events highlight the need for improved clinical trial design.