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癌症中铁死亡疗法的前景。

Prospects for ferroptosis therapies in cancer.

作者信息

Ubellacker Jessalyn M, Dixon Scott J

机构信息

Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Department of Biology, Stanford University, Stanford, CA, USA.

出版信息

Nat Cancer. 2025 Aug 18. doi: 10.1038/s43018-025-01037-7.


DOI:10.1038/s43018-025-01037-7
PMID:40826242
Abstract

Ferroptosis is a nonapoptotic form of cell death characterized by lethal membrane lipid peroxidation. This mechanism was first characterized in cancer cells well over a decade ago, and there is much enthusiasm for the concept that certain cancers may be treated by inducing ferroptosis. However, therapies that engage ferroptosis have yet to enter clinical testing. In this Review, we highlight the gap between our rapidly expanding knowledge of the ferroptosis mechanism and its translation into cancer therapies. We discuss the known challenges that may be slowing ferroptosis therapies from reaching the clinic.

摘要

铁死亡是一种非凋亡形式的细胞死亡,其特征是致命的膜脂质过氧化。这种机制早在十多年前就在癌细胞中首次被描述,并且人们对通过诱导铁死亡来治疗某些癌症的概念充满热情。然而,涉及铁死亡的疗法尚未进入临床试验。在本综述中,我们强调了我们对铁死亡机制迅速扩展的认识与其转化为癌症治疗方法之间的差距。我们讨论了可能阻碍铁死亡疗法进入临床的已知挑战。

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本文引用的文献

[1]
Endoplasmic reticulum-mitochondria contacts are prime hotspots of phospholipid peroxidation driving ferroptosis.

Nat Cell Biol. 2025-6

[2]
Glycosaminoglycan-driven lipoprotein uptake protects tumours from ferroptosis.

Nature. 2025-6-11

[3]
Cocrystal structure reveals the mechanism of FSP1 inhibition by FSEN1.

Proc Natl Acad Sci U S A. 2025-6-3

[4]
PCSK9 drives sterol-dependent metastatic organ choice in pancreatic cancer.

Nature. 2025-5-21

[5]
Activation of lysosomal iron triggers ferroptosis in cancer.

Nature. 2025-5-7

[6]
ALDH7A1 protects against ferroptosis by generating membrane NADH and regulating FSP1.

Cell. 2025-5-15

[7]
Ferroptosis spreads to neighboring cells via plasma membrane contacts.

Nat Commun. 2025-3-26

[8]
De novo lipogenesis protects dormant breast cancer cells from ferroptosis and promotes metastasis.

Redox Biol. 2025-3

[9]
Ferroptosis: when metabolism meets cell death.

Physiol Rev. 2025-4-1

[10]
Exogenous dihomo-γ-linolenic acid triggers ferroptosis via ACSL4-mediated lipid metabolic reprogramming in acute myeloid leukemia cells.

Transl Oncol. 2025-2

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