The EACR’s ‘Highlights in Cancer Research’ is a regular summary of the most interesting and impactful recent papers in cancer research, curated by the Board of the European Association for Cancer Research (EACR).
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Haldar, S.D. et al. Cancer Discovery. OF1–OF14. (2026).
doi: 10.1158/2159-8290.CD-25-2245
Summary of the findings
Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers, underscoring the need for novel strategies to intercept disease progression from precancer lesions. Pancreatic cancer is particularly well suited to immune interception because oncogenic KRAS mutations arise in the majority of precancer lesions. Furthermore, progression from precursor lesions to invasive cancer often occurs over many years and is accompanied by increasing immune suppression. This provides an opportunity to vaccinate individuals at high-risk before immune evasion and invasive disease develop.
In this study, we evaluated a mutant KRAS peptide vaccine in individuals at high risk for PDAC due to known familial predisposition and/or pathogenic germline variants. Vaccination was well tolerated and generated durable mutant KRAS-specific T cell responses for up to two years in those who had long-term samples available. Notably, pancreatic cystic lesions or IPMNs showed stabilization or regression more frequently among vaccinated participants than in a clinically comparable unvaccinated cohort in an exploratory analysis. Overall, these findings provide the first clinical evidence supporting the safety, immunogenicity, and feasibility of vaccine-based pancreatic cancer interception.
Future impact
These results establish a foundation for further evaluation of whether vaccination can eliminate or suppress pancreatic precursor lesions before they progress to invasive cancer. Ongoing studies will define how vaccine-induced T cells engage precursor lesions and identify biomarkers and rational combination strategies to enhance interception..
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