BRAF mutation

Overall, she had an unusual pattern of disease progression in molecularly low-risk CRC, indicating that delayed CNS metastasis can occur despite apparent systemic remission. These findings challenge current assumptions regarding CNS risk stratification in CRC and raise important questions about the need for individualized neurological surveillance strategies in selected patient subgroups.

To our knowledge, after review of the available literature, this appears to be the first reported case of recurrent PHPT with synchronous ipsilateral parathyroid adenoma/hyperplasia and multifocal PTC comprising three histological variants with distinct molecular alterations. This unique presentation underscores the necessity for comprehensive thyroid evaluation in PHPT patients, the utility of molecular profiling in establishing tumor clonality, and the importance of individualized surgical planning in complex endocrine neoplasia.

Strong agreement: it is recommended to perform systematic regional and remote extension assessment at diagnosis; PET-CT is the gold standard for remote assessment; isolated radiotherapy is not recommended for curative treatment; given the major risk of metastasis and the poor prognosis, alternatives to heavy destructive surgery should be considered in the rare cancer multidisciplinary tumor board; it is recommended to screen for NRAS, BRAF and KIT mutations, to identify possible treatment targets; reference imaging should be performed 3 months after end of treatment, using sinonasal and brain MRI and PET-CT; due to the risk of early recurrence, close follow-up is recommended during the first 2 years, then at least every 6 months up to 5 years postoperatively. Relative agreement: operable sinonasal mucosal melanoma should be treated by total macroscopic resection with negative margins followed by radiotherapy on the tumor bed; postoperative radiotherapy is recommended, to improve local control; neoadjuvant or adjuvant chemotherapy, other than immunotherapy or targeted therapy, is not recommended; for non-resectable and/or metastatic sinonasal mucosal melanoma, immunotherapy is the systematic first-line treatment; prophylactic lymph-node treatment is not recommended in N0 sinonasal mucosal melanoma; lymph-node surgery is recommended in N+ cases without remote metastasis, including cases of regional recurrence.

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