AKR1B10 Drives Lenvatinib Resistance in Hepatocellular Carcinoma by Suppressing Ferroptosis via NQO1/GPX4 Axis

Jiahao Jiang Bingkun Wang Qingbin Wang Xiaowu Ma Zhiqin Xie Lei Yang Chen-Wei Tang Hongkai Zhuang Wentao Wang Chang-Zhen Shang Ya-Jin Chen

Aug 2026 · Journal of Gastroenterology and Hepatology · Vol 41, pp. 3209 - 3223 · 1 citation · 40 references

Medicine

TL;DR

It is revealed that AKR1B10 inhibits ferroptosis in HCC through the NQO1/GPX4 axis, promoting acquired resistance to lenvatinib.

Abstract

Lenvatinib is utilized as a first‐line therapy for hepatocellular carcinoma (HCC); however, the emergence of resistance significantly impairs its clinical efficacy. Ferroptosis, a newly recognized form of cell death, has been implicated in tumor progression and treatment resistance. This study investigates the interaction between ferroptosis and lenvatinib resistance in HCC and explores the underlying mechanisms.

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