The crosstalk between autophagy and ferroptosis: what can we learn to target drug resistance in cancer?

Yulu Zhou; Yong Shen; Cong Chen; Xinbing Sui; Jingjing Yang; Linbo Wang; Jichun Zhou

doi:10.20892/j.issn.2095-3941.2019.0158

The crosstalk between autophagy and ferroptosis: what can we learn to target drug resistance in cancer?

Cancer Biol Med. 2019 Nov;16(4):630-646. doi: 10.20892/j.issn.2095-3941.2019.0158.

Authors

Yulu Zhou^{1

2}, Yong Shen³, Cong Chen^{1

2}, Xinbing Sui^{4

5

6}, Jingjing Yang^{1

2}, Linbo Wang^{1

2}, Jichun Zhou^{1

2}

Affiliations

¹ Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.
² Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou 310016, China.
³ Department of Breast Surgery, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China.
⁴ Department of Medical Oncology, Holistic Integrative Oncology Institutes and Holistic Integrative Cancer Center of Traditional Chinese and Western Medicine, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou 310012, China.
⁵ Department of Cancer Pharmacology, Holistic Integrative Pharmacy Institutes, College of Medicine, Hangzhou Normal University, Hangzhou 310012, China.
⁶ Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou 310012, China.

PMID: 31908884
PMCID: PMC6936238
DOI: 10.20892/j.issn.2095-3941.2019.0158

Abstract

Autophagy is a conserved intracellular degradation system that plays a dual role in cell death; thus, therapies targeting autophagy in cancer are somewhat controversial. Ferroptosis is a new form of regulated cell death featured with the iron-dependent accumulation of lethal lipid ROS. This pathway is morphologically, biochemically and genetically distinct from other forms of cell death. Accumulating studies have revealed crosstalk between autophagy and ferroptosis at the molecular level. In this review, we summarize the mechanisms of ferroptosis and autophagy, and more importantly, their roles in the drug resistance of cancer. Numerous connections between ferroptosis and autophagy have been revealed, and a strong causal relationship exists wherein one process controls the other and can be utilized as potential therapeutic targets for cancer. The elucidation of when and how to modulate their crosstalk using therapeutic strategies depends on an understanding of the fine-tuned switch between ferroptosis and autophagy, and approaches designed to manipulate the intensity of autophagy might be the key.

Keywords: Autophagy; cancer; crosstalk; drug resistance; ferroptosis.