KRAS G12

P2/3, N=465, Not yet recruiting, Jiangxi Kvvit Pharmaceutical Co., Ltd.

P3, N=338, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Sep 2027 --> May 2026

P2, N=86, Recruiting, Abbisko Therapeutics Co, Ltd | Not yet recruiting --> Recruiting

P1, N=140, Not yet recruiting, Clasp Therapeutics, Inc.

P1, N=24, Recruiting, Ruijin Hospital

Mouse embryonic fibroblasts transformed with KRASG12C also contain more saturated lipids than KRASG12D MEFs. Thus, activities of KRAS mutants depends on lipid acyl chain remodeling in an allele-specific manner.

This regimen is highly clinically accessible and may serve as a second-line treatment option when KRAS G12C-specific inhibitors are unavailable. Its clinical value requires further validation through large-sample prospective studies.

Furthermore, as a proof-of-concept, the sensing paradigm reliably discriminated KRAS-mutant patients from healthy donors in clinical plasma samples, showing good agreement with PCR-based analysis. The ABINS strategy provides a simple amplification-coupled and label-free colorimetric approach for mutation-associated ctDNA analysis, while broader validation in larger clinical cohorts and more representative ctDNA models will still be needed to further define its practical performance.

Further exploration revealed that, while WFS1 is regulated by the MAPK and PI3K/AKT pathways in MRTX1133-sensitive cells, acquired resistance is associated with downregulation of the E3 ubiquitin ligase Smurf1, leading to increased WFS1 protein stability. Overall, these results highlight WFS1 as an adaptive factor and potential therapeutic target in KRASG12D-driven malignancies, offering a novel approach to enhance the efficacy of KRASG12D inhibitors and overcome acquired resistance.

P1/2, N=94, Not yet recruiting, Gilead Sciences Inc.

P2/3, N=27, Not yet recruiting, Merck Sharp & Dohme LLC

P2, N=180, Recruiting, Verastem, Inc.