Albendazole induces ferroptosis through the USP7-GPX4 axis in B-cell acute lymphoblastic leukemia
Abstract
B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive hematological malignancy that still requires the development of novel therapeutic strategies. Here, leveraging a drug-repurposing strategy, we performed a high-throughput screen of 3008 U.S. Food and Drug Administration (FDA)-approved drugs and identified albendazole (ABZ), a benzimidazole anthelmintic, as a potent agent against B-ALL across multiple preclinical models. Mechanistically, ABZ directly binds ubiquitin-specific protease 7 (USP7) and triggers its autophagy-dependent destabilization, subsequently promoting the ubiquitin-proteasome-mediated degradation of glutathione peroxidase 4 (GPX4), thereby inducing ferroptosis in B-ALL. Our study revealed that USP7 directly interacts with and stabilizes GPX4 by removing K48-linked ubiquitin chains, and both proteins are markedly upregulated in B-ALL patients, correlating with poor survival. Collectively, we identify a previously unrecognized USP7-GPX4 axis that governs ferroptosis and show that ABZ, as a novel ferroptosis inducer, triggers ferroptosis by targeting this axis, supporting clinical repurposing of albendazole or therapeutic targeting of USP7-GPX4 to improve B-ALL outcomes.
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BibTeX
@article{wang2026albendazole,
title = {{Albendazole induces ferroptosis through the USP7-GPX4 axis in B-cell acute lymphoblastic leukemia}},
author = {Hao Wang and Tianwang Guan and Xiaonan Lin and Yingqi Qiu and Zhongjie Huang and Zhao Liang and Peiyun Liao and Honghao Zhang and Caiwen Ou and Yuhua Li},
journal = {Communications Biology},
year = {2026},
month = oct,
doi = {10.1038/s42003-026-11229-1},
url = {https://www.nature.com/articles/s42003-026-11229-1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Albendazole induces ferroptosis through the USP7-GPX4 axis in B-cell acute lymphoblastic leukemia
AU - Hao Wang
AU - Tianwang Guan
AU - Xiaonan Lin
AU - Yingqi Qiu
AU - Zhongjie Huang
AU - Zhao Liang
AU - Peiyun Liao
AU - Honghao Zhang
AU - Caiwen Ou
AU - Yuhua Li
PY - 2026
DA - 2026/10/27
JO - Communications Biology
DO - 10.1038/s42003-026-11229-1
UR - https://www.nature.com/articles/s42003-026-11229-1
AB - B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive hematological malignancy that still requires the development of novel therapeutic strategies. Here, leveraging a drug-repurposing strategy, we performed a high-throughput screen of 3008 U.S. Food and Drug Administration (FDA)-approved drugs and identified albendazole (ABZ), a benzimidazole anthelmintic, as a potent agent against B-ALL across multiple preclinical models. Mechanistically, ABZ directly binds ubiquitin-specific protease 7 (USP7) and triggers its autophagy-dependent destabilization, subsequently promoting the ubiquitin-proteasome-mediated degradation of glutathione peroxidase 4 (GPX4), thereby inducing ferroptosis in B-ALL. Our study revealed that USP7 directly interacts with and stabilizes GPX4 by removing K48-linked ubiquitin chains, and both proteins are markedly upregulated in B-ALL patients, correlating with poor survival. Collectively, we identify a previously unrecognized USP7-GPX4 axis that governs ferroptosis and show that ABZ, as a novel ferroptosis inducer, triggers ferroptosis by targeting this axis, supporting clinical repurposing of albendazole or therapeutic targeting of USP7-GPX4 to improve B-ALL outcomes.
SN - 2399-3642
ER -