RAS 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.

No local recurrence or distant metastasis occurred during the available follow-up period. Preliminary findings suggest that MWA may have favorable short-term efficacy and safety in the treatment of small RAS-mutated thyroid nodules.

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.

Daraxonrasib was associated with treatment-related adverse events of grade 3 or higher in one third of patients with previously treated RAS-mutated PDAC; antitumor activity was also reported. (Funded by Revolution Medicines; RMC-6236-001 ClinicalTrials.gov number, NCT05379985.).

Collectively, these findings suggest that ASXL1MUT AML may be more appropriately classified as intermediate risk in the context of LIT+VEN-based therapy, with the depth of impact influenced by the specific LIT backbone.

High-ratio patients exhibited enrichment for RAS mutations (p=0.046). The identified P16 deletion ratio threshold of 0.8 may guide precision risk-adapted therapy in pediatric ALL, but its clinical utility must be validated in larger, diverse cohorts before implementation.

Ultimately, RAS mutations drive monocytic differentiation of LSCs and venetoclax (VEN) resistance through BCL-2 family rewiring. Beyond AML, they are hallmark genetic lesions in juvenile myelomonocytic leukemia (JMML) and present in 15%-20% of pediatric acute lymphoblastic leukemia (ALL) cases. Here, we propose a comprehensive pathogenic model and targeted therapeutic framework focusing on RAS, MCL-1, BCL2L1 to overcome drug resistance and improve patient outcomes.

This work establishes a computational framework to build global models integrating all the available clinical parameters and assess their relevance with respect to stiffness, while they are usually explored separately. Similarly, we established spatial statistics techniques to interpolate and model the topographical information embedded in local stiffness maps.

P1, N=3, Completed, City of Hope Medical Center | Active, not recruiting --> Completed | Trial completion date: May 2027 --> Mar 2026 | Trial primary completion date: May 2027 --> Mar 2026

We evaluated RAS/MAPK targeting using the MEK1/2 inhibitor selumetinib in combination with the menin inhibitor revumenib. Our preclinical study suggests a potential targeted treatment combination for KMT2A-r and RAS pathway mutant leukemia, but one which will require further optimization. COG completed clinical trials AAML03P1, AAML0531, AAML1031 and C2961.

While these findings require validation in larger cohorts, they support a thymic origin for CASTLE and establish its molecular distinction from follicular-derived thyroid cancers. The immunogenic tumor landscape suggests that immune checkpoint inhibitors, particularly those targeting PD-1/PD-L1, may be a promising therapeutic strategy, alongside emerging targets for precision oncology.