ArticleJournal of cancer research and clinical oncology2026
Hypoxia-induced endoplasmic reticulum stress mediates lenvatinib resistance in hepatocellular carcinoma through the IRE1α-XBP1s-HIF1α pathway.
Article in Journal of cancer research and clinical oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
backgroundHepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths globally, with a dismal prognosis for advanced patients. Lenvatinib, a first-line anti-angiogenic agent, has improved clinical outcomes, but drug resistance remains a major unmet clinical need. Hypoxia, a hallmark of solid tumors, crosstalks with endoplasmic reticulum stress (ERS), yet their combined role in lenvatinib resistance in HCC remains undefined.
methodsTCGA and GEO datasets were analyzed for ERS-related gene expression and prognostic value. In vitro experiments were conducted in HepG2 and HCCLM3 cells under normoxic (21% O₂) or hypoxic (1% O₂) conditions. Cell viability, apoptosis, migration, and protein expression were assessed via standard assays. siRNA silencing and the ERS inhibitor 4-PBA were used for mechanistic validation.
resultsThe ERS marker GRP78 was significantly upregulated in HCC tissues and correlated with poor survival. Hypoxia induced ERS in HCC cells, promoting proliferation and migration while attenuating lenvatinib-induced apoptosis. Mechanistically, hypoxia induces activation of the IRE1α-XBP1s-HIF1α axis, and genetic silencing of this axis restores lenvatinib sensitivity. 4-PBA effectively reversed hypoxia-mediated drug resistance.
conclusionsHypoxia-induced ERS mediates lenvatinib resistance in HCC via the IRE1α-XBP1s-HIF1α pathway. Targeting this axis provides a promising strategy to overcome anti-angiogenic therapy resistance in HCC.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.