Base by Base5 Aug 2025

️ 97: Pancreatic Cancer Genomics: Insights from the COMPASS Trial

️ Episode 97: Pancreatic Cancer Genomics: Insights from the COMPASS Trial

In this episode of PaperCast Base by Base, we explore how integrated whole genome and transcriptome sequencing uncovers clinically relevant subtypes and molecular features in advanced pancreatic ductal adenocarcinoma (PDAC).

Study Highlights:

The COMPASS trial profiled 268 advanced PDAC patients, generating whole genome and RNA sequencing data before chemotherapy initiation. Distinct subgroups emerged, including KRAS wild-type cases with BRAF alterations and homologous recombination-deficient (HRD) tumors enriched for mutational signature SBS3 and high HRDetect scores. Patients with basal-like subtypes and elevated systemic inflammation (GRIm-S high) had significantly poorer outcomes, despite transcriptional signs of immune infiltration. KRAS allelic imbalance, especially major imbalances, associated with worse overall survival and higher prevalence of pre-existing diabetes.

Conclusion:

This large prospective genomic profiling effort reinforces the need for subtype-specific therapeutic strategies and shows how integrating molecular and clinical data can inform precision oncology in PDAC.

Reference:

Knox, J. J., Jang, G. H., Grant, R. C., Zhang, A., Ma, L., et al. (2025). Whole genome and transcriptome profiling in advanced pancreatic cancer patients on the COMPASS trial. Nature Communications, 16, 5919. https://doi.org/10.1038/s41467-025-60808-z

License:

This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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