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Review
. 2022 Apr 26:10:e13238.
doi: 10.7717/peerj.13238. eCollection 2022.

Exosomes and ferroptosis: roles in tumour regulation and new cancer therapies

Yixin Shi  1 , Bingrun Qiu  1 , Linyang Huang  1 , Jie Lin  1 , Yiling Li  1 , Yiting Ze  1 , Chenglong Huang  2 , Yang Yao  1
Affiliations
Review

Exosomes and ferroptosis: roles in tumour regulation and new cancer therapies

Yixin Shi et al. PeerJ. .

Abstract

Research on the biological role of exosomes is rapidly developing, and recent evidence suggests that exosomal effects involve ferroptosis. Exosomes derived from different tissues inhibit ferroptosis, which increases tumour cell chemoresistance. Therefore, exosome-mediated regulation of ferroptosis may be leveraged to design anticancer drugs. This review discusses three pathways of exosome-mediated inhibition of ferroptosis: (1) the Fenton reaction; (2) the ferroptosis defence system, including the Xc-GSH-GPX4 axis and the FSP1/CoQ10/NAD(P)H axis; and (3) lipid peroxidation. We also summarize three recent approaches for combining exosomes and ferroptosis in oncology therapy: (1) promoting exosome-inhibited ferroptosis to enhance chemotherapy; (2) encapsulating exosomes with ferroptosis inducers to inhibit cancers; and (3) developing therapies that combine exosomal inhibitors and ferroptosis inducers. This review will contribute toward establishing effective cancer therapies.

Keywords: Cancer therapies; Exosomes; Ferroptosis; Tumour regulation.

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Conflict of interest statement

The authors declare there are no competing interests.

Figures

Figure 1
Figure 1. Exosomes and ferroptosis in tumours.
(A) Mechanisms causing chemoresistance, (B) artificially modified agents targeting cancer therapies.
Figure 2
Figure 2. Overview of ferroptosis pathways.
(A) Iron metabolism, (B) ferroptosis defence systems (Xc-GSH-GPX4 signalling axis, FSP1/CoQ10/NAD(P)H signalling axis, and GCH1-BH4 signalling axis), (C) lipid peroxide regulation (Stockwell et al., 2017; Tang et al., 2021).
Figure 3
Figure 3. Exosome-mediated inhibition of ferroptosis and known regulatory mechanisms.
Figure 4
Figure 4. Strategies for using exosomes and ferroptosis in tumour therapies.
(A) Promoting exosome-inhibited ferroptosis to enhance chemotherapy. The dotted line indicates the intervention hypothesis, (B) encapsulate exosomes with ferroptosis inducers to inhibit cancers (Erastin@FA-Exo and Erastin /RB@Exos-CD47), (C) develop therapies that combine exosomal inhibitors and ferroptosis inducers (Wang et al., 2021).
See this image and copyright information in PMC

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