The biological underpinnings of therapeutic resistance in pancreatic cancer

Gregory L Beatty; Gregor Werba; Costas A Lyssiotis; Diane M Simeone

doi:10.1101/gad.348523.121

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.

Authors

Gregory L Beatty^#^{1

2}, Gregor Werba^#^{3

4}, Costas A Lyssiotis^#^{5

6

7}, Diane M Simeone^#^{3

4

8}

Affiliations

¹ Abramson Cancer Center; University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
² Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
³ Department of Surgery, New York University School of Medicine, New York, New York 10016, USA.
⁴ Perlmutter Cancer Center, New York University Langone Medical Center, New York, New York 10016, USA.
⁵ Department of Molecular and Integrative Physiology, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan 48109, USA.
⁶ Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan 48109, USA.
⁷ Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
⁸ Department of Pathology, New York University School of Medicine, New York, New York 10016, USA.

^# Contributed equally.

Abstract

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

Abstract

Publication types

MeSH terms

Grants and funding