NRAS G12

To substantiate the preclinical findings, the utility of MEKi in combination with the autophagy inhibitor hydroxychloroquine was analyzed in patients with KRASG12R mutated metastatic PDAC...Three patients had impressive disease control: two had stable disease of 11 and 22.7 months, and one achieved a partial response with an 83% decrease in tumor size that lasted for 8.9 months. Overall, this work highlights how systems-based approaches in precision medicine can uncover mechanistic insights to guide the identification of PDAC patients most likely to benefit from tailored therapeutic strategies.

This study establishes the first sexual dimorphism-aware phosphoproteomic resource for Ras-driven hepatocarcinogenesis, systematically characterizing conserved and sex-divergent phosphorylation networks. The findings provide preliminary molecular insights into gender disparities in HCC progression and may guide future therapeutic exploration.

NRAS proto-oncogene mutations were detected in 80% of cases, but clinical benefit occurred without mutation. Trametinib is an effective, safe, first-line therapy for KLA/GLA.

To our knowledge, there are no previous reports of end-organ improvement and sustained response to chemotherapy containing an anti-EGFR antibody in a patient with CRC complicated by DCBM and DIC. This case highlights the potential benefits of early and appropriate therapy even in critically ill patients with rare metastatic patterns.

The fetal barrier to transformation was enforced by the histone methyltransferase MLL3, and it could be overcome by cooperating mutations, such as NrasG12D. Heritable fetal protection against leukemic transformation may contribute to the low incidence of congenital and infant leukemias in humans.

The farnesyltransferase inhibitor tipifarnib blocked mutant HRAS-PI3K signaling and synergized with MEK inhibitors in HRAS-mutated cells, whereas KRASG12C inhibitors blocked mutant KRAS-MEK signaling and synergized with PI3K inhibitors in KRASG12C-mutated cells. Synergy was abolished in MEFs lacking all RAS proteins and in cancer cell lines in which nonmutated RAS family members were deleted. Our data highlight the critical role of wild-type RAS family members in supporting mutant RAS signaling and its importance as a therapeutic cotarget in RAS-mutated cancers.

P1, N=45, Recruiting, UNC Lineberger Comprehensive Cancer Center | Trial primary completion date: Aug 2025 --> Jul 2026

In addition to proliferation, MAPK signaling influences conversion by regulating Ngn2 activity. Our results highlight the need to tune therapeutic interventions within a non-monotonic landscape that is shaped by genetics and levels of gene expression.

Plasma cfDNA analysis using NGS is feasible and offers insights into alectinib resistance mechanisms. Early detection of resistance-associated mutations may guide personalized treatment strategies. Larger prospective studies are needed to validate these findings.

P1, N=25, Completed, Elicio Therapeutics | Active, not recruiting --> Completed | Trial completion date: Mar 2026 --> Sep 2024

siCdk1 and siAnln prevented cancer in a diethylnitrosamine/phenobarbital model, in which tumor formation is driven by mutagenesis and chemical injury...Given that siAnln was effective in several models, we validated Anln effects using Cre-lox, and found that histologic features of MASH and HCC development were independently reduced. This demonstrates that siRNAs are safe and effective in preventing HCC in a large panel of preclinical cancer models, and identify ANLN as an effective chemoprevention target.

Furthermore, this compound's effectiveness and safety were confirmed in both MH/NRASG12D BCP-ALL mouse model and MB patient-derived xenograft (PDX) model, outperforming conventional therapies. These results support the therapeutic potential of dual-pathway inhibition in MEF2D fusion (+) BCP-ALL and suggest CUDC-907 as a promising candidate for precision treatment in fusion-driven leukemias with similar molecular dependencies.