RAS mutation

P1/2, N=83, Recruiting, Virginia Commonwealth University | Trial completion date: May 2027 --> Jan 2031 | Trial primary completion date: May 2026 --> Dec 2029

Beyond oncology, MEK pathway modulation is under investigation in fibrotic, inflammatory, and developmental disorders, although clinical validation remains at an early stage. Building on more than a decade of use in BRAFV600 (ie, Val600)-mutant melanoma, MEK inhibitors continue to be refined through biomarker-guided combination strategies and exploration in additional cancers and non-oncological diseases.

P1, N=36, Recruiting, Children's Oncology Group | Trial completion date: Jun 2026 --> Mar 2028 | Trial primary completion date: Jun 2026 --> Mar 2028

Molecular analysis demonstrated BAP1 mutation and a novel fusion involving PDZRN3::BRAF. Our finding expands our current understanding of the molecular landscape and pathogenesis of BIMT.

Our study provides a holistic understanding of the fission yeast pheromone signalling network, explaining how RAS signalling propagates differently through two downstream pathways. Our PS mathematical model may serve as a valuable reference framework for analysing other RAS signalling systems.

P2, N=38, Recruiting, Emory University | Not yet recruiting --> Recruiting

KSR1 knockdown did not substantially affect ppERK responses to Type I½ RAF inhibitor (Encorafenib) in both cell types, whereas ppERK sensitivity slightly decreased for Type II RAFi (TAK-632) in MCF7 cells, aligning with simulations. The efficacy of MEKi (Cobimetinib) slightly increased in MCF7 cells following KSR1 knockdown but slightly decreased in PSN1 cells where higher MEKi concentrations were required to suppress ERK signaling, as predicted by the model. Our computational models predict, and experiments validate that in RAS-mutant cells, two conformation-specific RAF inhibitors used in combination suppress the ERK pathway more effectively than a combination of MEK and RAF inhibitors irrespective of KSR1 levels.

P1/2, N=90, Recruiting, Isofol Medical AB | N=60 --> 90

Our findings debate the WHO 50% mucin threshold, showing that tumors with 5-50% mucin exhibit comparable aggressiveness to classical MAC. Integrating molecular profiling with histology may improve risk stratification and guide tailored therapeutic strategies for mucinous CRC, regardless of mucin proportion.

Anti-EGFR monoclonal antibodies, cetuximab and panitumumab, have demonstrated survival benefit in selected patients, particularly those with left-sided, RAS wild-type tumors. We also discuss mechanisms of resistance such as pathway reactivation, receptor mutations, and epithelial-to-mesenchymal transition, alongside emerging approaches, including combination regimens, ctDNA-guided rechallenge, and genotype-specific inhibitors. Collectively, these insights highlight the evolving landscape of precision oncology in CRC and the importance of molecular stratification to optimize EGFR-targeted therapy and overcome resistance.

Sex influenced survival independently of tumor burden, indicating that sex-associated differences in lung cancer outcomes are likely driven by systemic or microenvironmental factors rather than tumor-intrinsic growth mechanisms.