RAS

This phase 3 study evaluated the efficacy and safety of daraxonrasib, a multiselective RAS(ON) inhibitor, in patients with previously treated metastatic pancreatic ductal adenocarcinoma (mPDAC). Patients were randomized to receive either daraxonrasib or investigator's choice chemotherapy. Results demonstrated significantly longer overall survival and progression-free survival with daraxonrasib compared to chemotherapy, both in the RAS G12 mutated population and the overall population. Daraxonrasib also showed a favorable safety profile, with a significantly lower rate of treatment discontinuation due to adverse events compared to chemotherapy.

This prospective observational study assessed the utility of circulating tumor DNA (ctDNA) for mutational profiling and dynamic monitoring in 33 patients with metastatic colorectal cancer receiving palliative chemotherapy. ctDNA was detected in most patients at baseline, revealing frequent mutations in APC, TP53, KRAS, and PIK3CA. Good concordance was observed between plasma ctDNA profiles and tissue data. Longitudinal analysis showed the emergence of acquired mutations, particularly RAS mutations under anti-EGFR therapy, and correlated high ctDNA levels with shorter overall survival. These findings highlight ctDNA's potential to guide personalized treatment strategies and monitor resistance.

This study investigated the utility of urinary extracellular vesicles (EVs) as a liquid biopsy source for colorectal cancer (CRC). Urinary EVs demonstrated superior purity and DNA quality compared to plasma and urinary cell-free samples. Detecting RAS/BRAF mutations in urinary EV-DNA after curative surgery allowed for minimal residual disease (MRD) identification. MRD positivity was strongly associated with an increased risk of recurrence and inferior overall survival. These findings suggest that urinary EV-DNA is a promising tool for postoperative monitoring and risk stratification in CRC patients.