RAS wild-type

P2, N=50, Recruiting, University of Wisconsin, Madison | Active, not recruiting --> Recruiting | N=25 --> 50 | Trial completion date: Jul 2026 --> Jul 2028 | Trial primary completion date: Jul 2026 --> Jul 2028

This case highlights the power of comprehensive molecular profiling and high-frequency ctDNA monitoring to capture tumor evolution and minimal residual disease. Importantly, it further demonstrates how MRD-guided surveillance enables a precise balance between fast-acting targeted therapy and the sustained effects of immunotherapy, providing a blueprint for individualized, context- driven treatment strategies in rare molecular subtypes of pancreatic cancer.

This study is the largest longitudinal analysis of KRASM testing conducted in Australia, with significant improvement in testing rates seen over the time period. Rates of KRASM and characteristics of Australian KRAS mt patients correspond with published literature.

P2, N=48, Active, not recruiting, University of Colorado, Denver | Trial completion date: Feb 2026 --> Feb 2027

P1, N=154, Recruiting, Coherus Oncology, Inc. | Trial completion date: May 2027 --> Jan 2028 | Trial primary completion date: May 2027 --> Jan 2028

Incorporating a structured diagnostic algorithm that recognizes rare subtypes and integrating comprehensive genomic profiling into routine practice represents a paradigm shift from non-stratified to mechanism-driven therapy in pancreatic cancer. This narrative review summarizes the clinicopathological characteristics, molecular landscapes, and therapeutic opportunities of rare PDAC subtypes, highlighting how precision medicine can reshape prognosis and treatment in a historically hard-to-treat disease.

Emerging immunotherapies targeting Claudin18.2 and CXCR4 offer hope to overcome tumor resistance. Together, these strategies underscore the promise of molecular stratification, synthetic lethality, and novel targets to improve pancreatic cancer survival.

This retrospective multi-center study included 600 RAS wild-type advanced CRC patients (development cohort: 420 patients from two centers; external validation cohort: 180 patients from an independent center) treated with EGFR inhibitors (cetuximab/panitumumab) plus anti-angiogenic agents (bevacizumab/fruquintinib/regorafenib) between 2018 and 2021. As a supplementary tool to current clinical guidelines, the model can partially address the problem of clinical response heterogeneity in combination therapy and provide simple decision support for clinicians in primary and secondary hospitals with limited detection conditions. However, the model has certain limitations in long-term prognostic prediction and needs to be further optimized and validated in larger, multi-center prospective cohorts before it can be translated into clinical practice of precision oncology.

Results of subcutaneous tumor and pulmonary metastasis models exhibited a similar conclusion to in vitro experiments. Butyrate reduces cetuximab efficacy in KRAS wild-type colorectal cancer through EGFR and AMPK-Wip1 signaling, and may represent a candidate predictive biomarker for treatment response.

Furthermore, compared with 3' end nucleotide derivative modifications, 5' end capping is more effective at increasing ribozyme stability and compatibility with in vitro preparations. These features underscore the promising potential of natural pistol ribozymes as advanced therapeutic nucleic acid molecules for targeting KRAS mutation-driven cancers and suggest a generalizable strategy for structure-guided, allele-specific RNA therapeutics.

P2, N=31, Not yet recruiting, Fudan University

P1, N=132, Recruiting, Conjupro Biotherapeutics, Inc. | Trial completion date: Dec 2025 --> Aug 2027 | Trial primary completion date: Jun 2025 --> May 2027