Targeting ferroptosis in pancreatic cancer: a double-edged sword

Xin Chen; Rui Kang; Guido Kroemer; Daolin Tang

doi:10.1016/j.trecan.2021.04.005

Targeting ferroptosis in pancreatic cancer: a double-edged sword

Trends Cancer. 2021 Oct;7(10):891-901. doi: 10.1016/j.trecan.2021.04.005. Epub 2021 May 20.

Authors

Xin Chen¹, Rui Kang², Guido Kroemer³, Daolin Tang⁴

Affiliations

¹ Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, The Third Affiliated Hospital, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China; Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China; Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA.
² Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: rui.kang@utsouthwestern.edu.
³ Centre de Recherche des Cordeliers, Equipe Labéllisée par la Ligue Contre le Cancer, Université de Paris, Sorbonne Université, INSERM U1138, Institut Universitaire de France, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, 94800 Villejuif, France; Pôle de Biologie, Hôpital Européen Georges Pompidou, Assistance Publique - Hôpitaux de Paris, 75015 Paris, France; Suzhou Institute for Systems Biology, Chinese Academy of Sciences, Suzhou, China; Department of Women's and Children's Health, Karolinska University Hospital, 17176 Stockholm, Sweden. Electronic address: kroemer@orange.fr.
⁴ Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, The Third Affiliated Hospital, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China; Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: daolin.tang@utsouthwestern.edu.

PMID: 34023326
DOI: 10.1016/j.trecan.2021.04.005

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains an aggressive malignancy with a 5-year survival rate below 10%. Its unique genetic makeup and tumor microenvironment produce a lack of response to current treatments, including chemotherapy, radiotherapy, and immunotherapy. Recent preclinical studies have revealed that ferroptosis, an iron-dependent form of nonapoptotic cell death driven by unrestricted lipid peroxidation, may be an attractive therapeutic goal in PDAC. Understanding the dual role of ferroptotic cell death in both promoting and suppressing tumor immunity, as well as its integrated regulatory mechanisms and signaling pathways, may lead to more effective treatment designs for clinical trials of PDAC and may minimize or delay the emergence of drug resistance or side effects.

Keywords: cell death; ferroptosis; pancreatic cancer; redox signaling; therapy resistance; tumor microenvironment.

Publication types

Review

MeSH terms

Carcinoma, Pancreatic Ductal* / drug therapy
Ferroptosis*
Humans
Immunotherapy
Pancreatic Neoplasms* / drug therapy
Tumor Microenvironment