Genetics and Biology of Pancreatic Ductal Adenocarcinoma

Authors

Haoqiang Ying
Alec C Kimmelman
Nabeel Bardeesy
Raghu Kalluri
Anirban Maitra
Ronald A DePinho

Publication Date

1-7-2025

Journal

Genes Development

DOI

10.1101/gad.351863.124

PMID

39510840

PMCID

PMC11789498

PubMedCentral® Posted Date

1-1-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Pancreatic ductal adenocarcinoma (PDAC) poses a grim prognosis for patients. Recent multidisciplinary research efforts have provided critical insights into its genetics and tumor biology, creating the foundation for rational development of targeted and immune therapies. Here, we review the PDAC genomic landscape and the role of specific oncogenic events in tumor initiation and progression, as well as their contributions to shaping its tumor biology. We further summarize and synthesize breakthroughs in single-cell and metabolic profiling technologies that have illuminated the complex cellular composition and heterotypic interactions of the PDAC tumor microenvironment, with an emphasis on metabolic cross-talk across cancer and stromal cells that sustains anabolic growth and suppresses tumor immunity. These conceptual advances have generated novel immunotherapy regimens, particularly cancer vaccines, which are now in clinical testing. We also highlight the advent of KRAS targeted therapy, a milestone advance that has transformed treatment paradigms and offers a platform for combined immunotherapy and targeted strategies. This review provides a perspective summarizing current scientific and therapeutic challenges as well as practice-changing opportunities for the PDAC field at this major inflection point.

Keywords

Carcinoma, Pancreatic Ductal, Humans, Pancreatic Neoplasms, Tumor Microenvironment, Animals, Immunotherapy, cancer-associated fibroblast, immune regulation, kras, pancreatic cancer, targeted therapy, tumor heterogeneity, tumor microenvironment

Published Open-Access

yes

Recommended Citation

Ying, Haoqiang; Kimmelman, Alec C; Bardeesy, Nabeel; et al., "Genetics and Biology of Pancreatic Ductal Adenocarcinoma" (2025). Faculty, Staff and Student Publications. 4337.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4337