Hypoxia-induced endoplasmic reticulum stress mediates lenvatinib resistance in hepatocellular carcinoma through the IRE1α-XBP1s-HIF1α pathway
Chong Zhang, Yuxin Jiang, Jiatao Liu, Guoping Sun, Hanqing Yu · 2026
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Description
Chong Zhang and co-authors trace why liver tumors stop responding to a front-line drug. The drug, lenvatinib, starves tumors by cutting their blood supply, yet resistance grows. Low oxygen inside tumors and stress in the cell's protein workshop were both suspects. The team checked gene data from patients, then ran cell experiments in normal and low oxygen.
A stress marker was high in tumors and tied to worse survival. Low oxygen switched the stress response on, helped cells grow and move, and blunted the drug's killing. A three-link chain of proteins carried the effect. Silencing that chain, or adding a stress blocker, restored the drug's power. The authors propose targeting this chain to rescue treatment when oxygen runs low.
Catalog record
| CREATOR | Chong Zhang, Yuxin Jiang, Jiatao Liu, Guoping Sun, Hanqing Yu |
|---|---|
| YEAR | 2026 |
| COLLECTION | PAPERS |
| FORMAT | TXT |
| FILE SIZE | 47 KB |
| VERSION | 1.0 |
| LICENSE | CC BY 4.0 |
| RIGHTS | CC BY |
| SOURCE | Europe PMC |