Coexistence of TP53 and KRAS mutations identifies a molecular subset of biliary tract cancer with poor overall survival after first-line immunochemotherapy
A specific genetic mutation combination in bile duct cancer may predict poor immunotherapy response, guiding better treatment selection.
In 1,875 biliary tract cancer patients from Japan's national C-CAT genomics database, co-occurring TP53 and KRAS mutations identified the molecular subgroup with the worst outcomes, with numerically shorter OS when treated with ICI+chemotherapy vs chemotherapy alone (11.8 vs 15.9 months). While the treatment interaction was not statistically significant, these findings suggest TP53/KRAS co-mutation may be a predictive negative biomarker for ICI benefit warranting prospective validation.
What the study was
- Study design
- Retrospective genomic cohort (national database)
- Population
- Biliary tract cancer patients treated with GC or GC+ICI (C-CAT national Japan genomics database)
- Sample size
- 1875
- Category
- Genomics/Precision Medicine
- Maturity
- Exploratory
- Journal
- European Journal of Cancer
Why it surfaced
Large national genomic database (n=1875 BTC) providing genomic biomarker data for ICI treatment selection in a cancer with rapidly evolving immunotherapy landscape; C-CAT database provides population-level validity; hypothesis-generating for prospective confirmation
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