KRAS (KRAS proto-oncogene GTPase)

P2, N=34, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2026 --> Feb 2027

P1, N=54, Recruiting, Astellas Pharma Global Development, Inc. | Not yet recruiting --> Recruiting

P1, N=312, Active, not recruiting, Daiichi Sankyo | Recruiting --> Active, not recruiting

Co-occurring genetic alterations with RAS mutations markedly increased the risk of malignancy compared with isolated RAS mutations (Fisher's exact test, two-tailed p = 0.0026) and were associated with more aggressive tumor phenotypes, whereas isolated RAS mutations were more common in indolent neoplasms. Comprehensive molecular profiling is essential for accurate risk stratification and management of indeterminate thyroid nodules.

Adagrasib monotherapy yielded a median PFS of 4.4-5.6 months, an OS of 10-19.8 months, and an ORR of 19-23%, while its combination with cetuximab reported a PFS of 6.9 months, an OS of 13.4-15.9 months and an ORR of 34-46%...When combined with panitumumab, 960 mg sotorasib demonstrated better results with a PFS of 5.6-5.7 months, OS of 15.2 months and an ORR of 12.5-30%. Similarly, divarasib monotherapy led to a PFS of 5.6-6.9 months and an ORR of 20%, while its combination with cetuximab resulted in a PFS of 8.1 months and an ORR of 62.5%. Combination therapy of olomorasib and MK-1084, which are new-generation KRAS p.G12C (c.34G > T) inhibitors, with cetuximab also demonstrated highly promising efficacy with ORR of 38-44% and 50%, respectively...Initial results of KRAS-G12C inhibitors appear highly promising when they are combined with anti-EGFR therapy compared to historical therapeutic agents indicated for patients with chemotherapy-refractory CRC. Encouraging benefits warrant frontline trials with these novel therapeutics.

The patient therefore underwent adjuvant carboplatin/paclitaxel chemotherapy followed by vaginal brachytherapy and has remained recurrence-free for five years. This case demonstrates molecular classification of an unusual histological type of EC exhibiting an extremely short-term risk of early distant metastasis and its implication on aggressive adjuvant therapeutical approach. It, furthermore, exemplifies the pronounced heterogeneity of the NSMP subgroup.

P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Jan 2027

P2, N=22, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Jan 2027

P1, N=750, Active, not recruiting, Eli Lilly and Company | Recruiting --> Active, not recruiting

Predicted biomass flux showed enzyme knockdowns reduced growth across both conditions, but CCM models indicated a protective effect against perturbation. Overall, simulations illustrated CCM enhances the metabolic adaptability of KRAS-mutant CRC cells to perturbations, emphasizing the importance of including TME components in metabolic modeling and therapeutic development and suggesting that targeting tumor-CAF metabolic interactions may improve treatment strategies.