The biological underpinnings of therapeutic resistance in pancreatic cancer

Genes Dev. 2021 Jul 1;35(13-14):940-962. doi: 10.1101/gad.348523.121. Epub 2021 Jun 11.


Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality in the United States and has only recently achieved a 5-yr survival rate of 10%. This dismal prognosis reflects the remarkable capacity of PDAC to effectively adapt to and resist therapeutic intervention. In this review, we discuss recent advances in our understanding of the biological underpinnings of PDAC and their implications as targetable vulnerabilities in this highly lethal disease.

Keywords: PDAC; genetics; metabolism; microbiome; pancreatic cancer; pancreatic tumor microenvironment; targeted therapy; therapeutic resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Carcinoma, Pancreatic Ductal* / drug therapy
  • Carcinoma, Pancreatic Ductal* / genetics
  • Carcinoma, Pancreatic Ductal* / pathology
  • Drug Resistance, Neoplasm / genetics
  • Humans
  • Molecular Targeted Therapy / adverse effects
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / genetics
  • Tumor Microenvironment