KRAS wild-type

KRAS mutations are associated with aggressive recurrence patterns and a poor prognosis for patients with CRLM. However, survival following local therapy for recurrence appeared less pronounced regardless of KRAS status.

Summary and Outlook: An understanding of the crosstalk of these molecular pathways will be critical in designing rational therapeutic strategies. Genetics, metabolism, and microenvironmental integration may open a path toward combinatorial therapies that would resensitize PDAC to apoptosis and overcome resistance to current treatments.

The substantial hereditary and potentially actionable molecular burden supports universal germline testing and comprehensive tumour genomic profiling, particularly in younger patients and in KRAS wild-type disease. PARP inhibitors should be described as improving progression-free survival or disease-control outcomes in selected BRCA-mutated metastatic PDAC rather than as having established a statistically significant overall survival benefit.

This study is the first to examine p27 localization in WT KRAS CRC. The observed association between WT KRAS expression and cytoplasmic p27 localization highlights a potential mechanism contributing to tumour progression through altered p27 function.

P1/2, N=58, Completed, Associacio Per A La Recerca Oncologica | Phase classification: P=N/A --> P1/2 | --> Completed

We report a case of metastatic CRC that achieved CR following second-line treatment with FOLFIRI plus ramucirumab after disease progression on first-line FOLFOX plus panitumumab therapy...In the present case, a watch-and-wait strategy was selected to prioritize organ preservation. Given the lack of consensus, further investigation is required to define the optimal strategy for patients achieving CR.

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.

The NTZ-AG regimen demonstrated meaningful anti-tumor activity and an acceptable safety profile as first-line therapy for unselected advanced pancreatic cancer patients, providing a rational basis for larger randomized controlled trials. This trial was registered at the Chinese Clinical Trial Register (ChiCTR) under the registration number ChiCTR2300072843 having URL https://www.chictr.org.cn/showprojEN.html?proj=198791.

Although recent advances have led to covalent inhibitors such as Sotorasib and Adagrasib for the KRAS G12C mutation, effective therapies for other common variants, particularly KRAS G12D, which is highly prevalent in aggressive pancreatic cancers, remain limited...To further validate the predictive capability of the models, two compounds identified as high-confidence candidates, Cobimetinib and Etrasimod, were selected for experimental evaluation...While additional biochemical and pathway-level studies are required to confirm direct target engagement, these results support the model's utility in prioritizing candidate compounds with allele-specific activity profiles. Overall, this study provides a data-driven framework for identifying potential KRAS-targeted therapies and highlights the value of integrating machine learning predictions with experimental validation.

The minimally invasive anatomical approach allowed precise vascular control and achievement of oncologically adequate margins in a technically demanding central segment. Larger clinical series are needed to define optimal management strategies and long-term oncologic outcomes in this setting.

P1, N=18, Recruiting, Joint Biosciences Ltd.

P2/3, N=574, Recruiting, SUNHO（China）BioPharmaceutical CO., Ltd. | N=90 --> 574 | Trial completion date: Jul 2028 --> Jul 2029 | Trial primary completion date: Jul 2026 --> Jul 2028