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Updated: Oct 17, 2025
Pancreatic Tissue Dissection to Isolate Viable Single Cells
Published on: May 26, 2023
[Molecular classification of pancreatic cancer]
1II. Sz. Patológiai Intézet, Semmelweis Egyetem, Budapest, Hungary. jtimar@gmail.com.
Abstract:
Pancreatic cancer is a malignancy with outstandingly poor prognosis caused by several factors among which one is that it is predominated by mutant KRAS oncogene. Genomic studies revealed that clinically useful therapy targets are present only in the DNA repair deficient subgroup and in the minor wild type KRAS-carrying group. However, phylogenetic studies defined four molecular subgroups of pancreatic cancer among which the immunogenic progenitor form could well be the target of immunotherapies. Furthermore, this group may well be the one characterized by DNA repair deficiency and high tumor mutational burden. Furthermore, the majority of familiar pancreatic cancers could also be found in this latter subgroup. Unfortunately, the G12C mutation of KRAS in pancreatic cancer is rare, therefore pancreatic cancer patients could not benefit from the recent revolution of KRAS target therapies.
Insights
Pancreatic cancer, often driven by KRAS mutations, has limited therapy targets. Identifying specific molecular subgroups may unlock new immunotherapy and DNA repair-targeted treatments.
Area of Science:
- Oncology
- Genetics
- Immunotherapy
Background:
- Pancreatic cancer exhibits a poor prognosis, largely due to the prevalence of the KRAS oncogene.
- Current therapeutic strategies are limited, with targets identified mainly in DNA repair-deficient or wild-type KRAS subgroups.
- The KRAS G12C mutation, a target for recent therapies, is rare in pancreatic cancer.
Purpose of the Study:
- To explore molecular subgroups of pancreatic cancer for novel therapeutic targets.
- To investigate the potential of immunotherapies for specific pancreatic cancer subtypes.
- To correlate DNA repair deficiency and familial cancer predisposition with molecular subgroups.
Main Methods:
- Phylogenetic analysis to define molecular subgroups.
- Genomic studies to identify therapy targets.
- Analysis of KRAS mutation status and its clinical implications.
Main Results:
- Four distinct molecular subgroups of pancreatic cancer were identified.
- The immunogenic progenitor subgroup shows potential for immunotherapy.
- This subgroup may also exhibit DNA repair deficiency and high tumor mutational burden, and includes most familial pancreatic cancers.
- The KRAS G12C mutation is infrequent, limiting the benefit of targeted therapies.
Conclusions:
- Pancreatic cancer classification into molecular subgroups offers new therapeutic avenues.
- The immunogenic progenitor subgroup is a promising candidate for immunotherapy development.
- Targeting DNA repair deficiencies and exploring immunogenic subtypes are crucial for advancing pancreatic cancer treatment.
