BRAF mutation

Our work demonstrates that BET inhibition improves MAPK signaling blockade through profound epigenetic reprogramming of core transcription factor circuits. These findings provide a preclinical rationale for the evaluation of BET + BRAF + EGFR inhibition in patients with treatment-refractory BRAFV600E metastatic CRC (NCT06102902).

Furthermore, in these tumors, we provide preliminary evidence to support the prognostic relevance of RAPGEF1 expression in patients lacking RAS or BRAF mutations. Together with other recent studies, these data suggest that germline variation influencing RAS activation may play a key role in nevus development and melanoma risk.

These findings expand the molecular spectrum of thyroblastoma beyond the canonical DICER1-driven paradigm and suggest that DICER1-wildtype cases may represent a distinct biological subgroup. The identification of alterations affecting TERT and MAPK pathways highlights potential therapeutic vulnerabilities and supports the clinical value of comprehensive genomic profiling in ultra-rare thyroid malignancies.

Here, we analyzed paired baseline and end-of-treatment samples from 40 patients treated with the RAS inhibitor daraxonrasib and identified recurrent alterations in 18 cases...We then identified a TCI that targets RAS Y64 mutants and combination therapies to target resistance driven by kinase-dead BRAF. These findings uncover convergent resistance mechanisms that undermine the molecular glue function and offer a mechanistic blueprint for enhancing therapeutic efficacy in RAS-driven malignancies.

Human and murine models resistant to combined belvarafenib and cobimetinib exhibited elevated levels of ATF4 and MTHFD2 and were sensitive to sapanisertib. This study provides promising treatment opportunities for patients with non-BRAF-mutant melanomas, or those who relapse following belvarafenib and cobimetinib combination therapy.

P1, N=6, Recruiting, Ipsen | Not yet recruiting --> Recruiting

P1/2, N=30, Active, not recruiting, Medical Center - University Of Freiburg | Recruiting --> Active, not recruiting

ETBF promotes acute colitis in mice expressing different oncogenic mutations, but with distinct patterns of colonic epithelial cell damage and inflammation dependent on host oncogene context.

P1/2, N=420, Recruiting, BioNTech SE

These findings suggest that incorporating ancestry into screening, trials, and precision oncology may improve equity, though outcome-linked prospective studies and implementation research are warranted.

The rates of immune-related adverse events were similar to those reported in the literature, but there was a lower therapy discontinuation rate. This might be due to more appropriate managing of emerging immunotherapy toxicities.