KRAS (KRAS proto-oncogene GTPase)

P=N/A, N=101, Completed, University Hospital, Rouen | Unknown status --> Completed | Phase classification: P3 --> PN/A

P3, N=160, Active, not recruiting, Amgen | Trial completion date: Jan 2026 --> May 2026

Collectively, our findings reveal that the USP20-RAB8A-GLUT1 axis regulates glucose uptake and metabolic reprogramming in PDAC, thereby inhibiting tumor growth and metastasis. Targeting this signaling axis provides a novel insight into metabolic therapy for pancreatic cancer.

P3, N=453, Active, not recruiting, Eli Lilly and Company | Trial completion date: Dec 2025 --> Dec 2026

P2, N=28, Completed, Canadian Cancer Trials Group | Active, not recruiting --> Completed

This study provides a comprehensive genomic overview of AM, highlighting recurrent alterations in the MAPK and cell cycle pathways, and potential demographic-specific molecular signatures. These findings support the need for expanded molecular profiling to improve prognostic accuracy and identify targets for future therapy.

RAF1 is a key, non-redundant vulnerability in KRAS-driven lung adenocarcinoma. Co-targeting ARAF, EGFR, or DDR1 provides no additional therapeutic benefit in established disease. The absence of adverse effects from ARAF co-deletion suggests that RAF1 degraders with partial cross-activity towards ARAF are likely to be safe. These findings provide a strong preclinical rationale for developing RAF1-targeted degradation as a monotherapy for these malignancies.

Here, we show that the KRAS G12C inhibitor LY3499446 induces CIN in KRAS -mutant NSCLC cell lines...In the presence of Aurora Kinase A inhibition, cyclin B1 stabilization delays mitotic exit and diverts cell fate from mitotic slippage or division toward mitotic catastrophe. Together, our findings identify CIN as a predictive marker of response to combined KRAS G12C and Aurora Kinase A inhibition, providing mechanistic rationale to enhance the therapeutic window of AURKA inhibitors when used with targeted therapies.

PRMT5 inhibitor activity is independent of TKI exposure, driver alteration, and SDMA expression and enhanced by addition of TKI. These findings support clinical evaluation of PRMT5 inhibitor + TKI combinations for advanced NSCLC.

This study underscored the clinical and genomic heterogeneity of GI-NEC and highlighted the need to integrate genomic and clinical data to achieve personalized medicine. MYC amplification and KRAS alterations may serve as valuable predictors of treatment response and prognosis in patients with GI-NEC.

Persons who have a more pro-inflammatory lifestyle may have an increased recurrence risk (IRR 1.21, 95% CI 0.97-1.52), which was most pronounced for persons with MSS and KRAS or PIK3CA wildtype tumours (IRR 1.31, 95% CI 0.90-1.90 and IRR 1.30, 95% CI 0.98-1.71, respectively). Our results suggest that associations between the LIS and recurrence might differ based on molecular tumour characteristics.

Gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX (FFX) therapies are widely used to treat advanced pancreatic ductal adenocarcinoma (PDAC)...In Japanese real-world data, GnP showed superior TTP compared with FFX for advanced PDAC. TP53 status may serve as a prognostic biomarker in patients receiving GnP therapy.