RAS wild-type

Our findings directly inform clinical guidelines, address gaps in current therapeutic decision-making. Durvalumab or pembrolizumab combined with GC are optimal first-line regimens for advanced BTC, balancing survival benefits and safety. Sintilimab plus anlotinib combined with GC demonstrates superior PFS but requires further validation. While EGFR inhibitors plus chemotherapy demonstrate potential in KRAS wild-type patients, confirmation in large-scale RCTs is required. PD-L1 expression may represent a promising predictive biomarker for response to PD-1 inhibitor therapy.

The exploratory analysis of FIRE-3 suggests that the efficacy of cetuximab combined with FOLFIRI in RAS wild-type mCRC is related to sex and primary tumor sidedness. The results support the inclusion of patient sex into the design of future trials.

The chemotherapy history included fluoropyrimidine (101 patients, 100%), oxaliplatin (95 patients, 94.1%), irinotecan (82 patients, 81.2%), anti-vascular endothelial growth factor antibody (92 patients, 91.1%) and anti-epidermal growth factor receptor antibody (41 patients, accounting for 87.2% of the RAS wild-type subgroup). The results of the present study suggested that TAS-102 combined with bevacizumab in subsequent treatment may have greater efficacy in rectal cancer than in colon cancer, possibly due to the lower frequency of liver metastases in rectal cancer. However, this finding is exploratory and requires further validation via larger prospective studies.

Consequently, the patient was diagnosed with pancreatic medullary carcinoma. To our knowledge, only 33 cases of pancreatic medullary carcinoma have been reported to date, and this is the first report to describe its cytological features.

Future outlooks are outlined with near-term biomarker-drug hypotheses for microsatellite-stable (MSS)-iCMS3 and high fibrosis tumors and key gaps to close for clinical translation. This review outlines a roadmap for precision medicine in colorectal cancer by leveraging the iCMS/IMF framework to integrate pathology and digital pathology, molecular diagnostics, and therapy mapping with FAP-targeted imaging and therapy.

This study suggests codon 13 KRAS mutations may be associated with LR in LARC. However, given the small number patients and events, these findings should be cautiously interpreted until confirmed by larger studies. Preoperative genetic testing for KRAS mutations is suggested to enhance risk stratification.

The addition of targeted therapy based on biomarker status (e.g., panitumumab in KRAS-wildtype tumors) demonstrated significant improvements in DFS and OS...Its efficacy is highly dependent on careful patient selection based on disease stage and molecular characteristics. Future research should focus on randomized trials in high-risk populations and the integration of personalized treatment approaches.

P3, N=377, Active, not recruiting, Institut du Cancer de Montpellier - Val d'Aurelle | Trial completion date: Sep 2025 --> Sep 2026

These include oncogene driver alterations (gene fusions and mutations) and mutations in genes of the HR pathway. Targeted therapy strategies for PDAC rely on molecular testing beyond RAS, but further research is needed to identify new therapeutic approaches that improve outcomes in PDAC.

P1, N=2, Active, not recruiting, Roswell Park Cancer Institute | Trial primary completion date: Dec 2025 --> Jul 2025

One patient had pleomorphic Sertoli cells associated with TP53 variants and very poor prognosis with early recurrence after complete initial surgery of a stage IA tumor. These data highlight the biological relationship between SLCTs and their heterologous elements, and the clinical usefulness of identifying pathogenic variants (ie, TERT and TP53), although this last point needs to be confirmed in a larger series.

CMS4 might be an additional biomarker of anti-EGFR treatment efficacy in RAS (and BRAF) WT mCRC.