KRAS G13

Furthermore, co-occurring RAS pathway mutations leading to increased wild-type RAS activation are enriched in codon 13 mutant tumors. Consistent with a role for wild-type RAS(ON) signaling, combination of RMC-8839 with a RAS(ON) multi-selective inhibitor resulted in deeper inhibition of KRAS G13C-mutant xenograft tumor growth than either inhibitor alone.

To determine combination partners that enhance RAS(ON) mutant-selective inhibition, a drug repurposing screen revealed that KRASG13C models are selectively vulnerable to chemotherapy. Combination of docetaxel with RMC-8839 demonstrated robust anti-proliferative activity in KRASG13C-driven NSCLC models in vitro and in vivo.

We present a 57-year-old man with KRAS G13D-mutant, liver-dominant metastatic rectal adenocarcinoma and recurrent fluoropyrimidine-associated coronary vasospasm precluding 5-fluorouracil and capecitabine. After multimodal first-line therapy and regorafenib, trifluridine/tipiracil (TAS-102) plus bevacizumab was initiated and integrated with liver-directed treatments for oligoprogressive disease. This combined strategy achieved approximately 16.6 months of disease control, substantially exceeding the median progression-free survival reported in the SUNLIGHT trial, with manageable hematological toxicity and preserved performance status. This case highlights the value of TAS-102 plus bevacizumab combined with focal liver-directed therapy as a feasible long-term strategy for selected patients with oligoprogressive mCRC when fluoropyrimidines cannot be used.

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.

P1, N=76, Not yet recruiting, Beijing Youcare Kechuang Pharmaceutical Technology Co., Ltd.

P1/2, N=265, Recruiting, Blueprint Medicines Corporation

P3, N=590, Recruiting, Revolution Medicines, Inc. | N=420 --> 590

We review reports of the interaction of cathepsin B with trypsinogen in the pancreas and caspases in inflammasomes and the potential effect of premature activation of trypsin on immune evasion of G12R mutants. We summarize our observations and literature review in a schematic describing the potential role inflammation and the actions of cathepsin B, trypsin, and caspases on the immune evasion of KRas and related Ras family gene products.

KRAS mutations-particularly exon 2 alterations-are associated with inferior OS in CRC. Among KRAS-mutant subtypes, G12A and K117N confer the poorest prognosis, supporting the clinical value of subtype-level risk stratification.

In both univariate and multivariate analysis, detection of mutant KRAS G12, Q61, or G13 in baseline ctDNA by whole-genome sequencing was superiorly predictive of worse OS over pre-therapy serum CA 19-9. Ultra-deep sequencing demonstrates robust detection of pertinent KRAS mutations that support improved prognostic stratification for patients with localized PDAC, demonstrating the potential value of advanced liquid biopsy technology to tailor treatment decisions and improve patient outcomes.

Hence, trametinib constitutes a promising precision therapeutic approach for severe KRAS-related NOFs.

P1, N=364, Recruiting, Astellas Pharma Inc