ArticleThe Journal of clinical investigation2022
HIF inhibitor 32-134D eradicates murine hepatocellular carcinoma in combination with anti-PD1 therapy.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 99 citations in OpenAlex.
- HIF-1-mediated PPME1 expression promotes breast cancer progression via AKT activation and β-catenin recruitment.The Journal of clinical investigation · 2026Article
- Understanding the role of hypoxia inducible factors in liver fibrosis and future therapeutic applications.iLIVER · 2026Review
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- Targeting conserved domains of hypoxia-inducible factors for cancer therapy.The Journal of experimental medicine · 2026Article
- Depleting HIF‑1α attenuates the progression of osteosarcoma, but tumorigenicity is sustained through HIF‑independent pathways.Oncology reports · 2026Article
- Hypoxic Tumor Microenvironment Targeting: Opportunities and Challenges for Pancreatic Cancer Immunotherapy.International journal of molecular sciences · 2026Review
- Sohlh2 inhibited the angiogenesis of hepatocellular carcinoma through the HIF-1α/VEGFA pathway.Translational oncology · 2026Article
- Trefoil Factor-3 Is a Hypoxia-Triggered Pro-Tumorigenic Factor in Hepatoblastoma.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Molecular stress and neurovascular injury in the diabetic retina.The Journal of clinical investigation · 2026Review
- Sublethal heat stress synergizes with the tumor microenvironment to drive recurrence of hepatocellular carcinoma after thermal ablation: mechanisms, molecular predictors, and targeted interventions.Cell biology and toxicology · 2026Review
- Spatiotemporal dynamics of tumor-associated neutrophils: bridging the gap between cancer progression and immunotherapy.Molecular cancer · 2026Review
- A novel multiplex RNAi therapy simultaneously targets Hif1a and Hif2a to defy retinal degeneration in two models of AMD.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Hypoxic microenvironment in cancer: role in metabolic reprogramming.Frontiers in oncology · 2026Review
- Hypoxia-driven tumor immune escape: mechanisms and therapeutic opportunities.Frontiers in immunology · 2026Review
- Understanding Immune Cell Adaptation to Tumor Hypoxia for Maximized Therapeutic Efficacy of Immunotherapy: Biology and Non-invasive Imaging Application.Cancer research and treatment · 2026Review
- Next Generation DNA Damage Response Inhibitors: Harnessing Nanocarriers and Tumor Microenvironment for Precision Cancer Therapy.Oncology research · 2026Review
- Overcoming resistance to antibody-drug conjugates: from mechanistic insights to cutting-edge strategies.Journal of hematology & oncology · 2025Review
- Immunometabolism: crosstalk with tumor metabolism and implications for cancer immunotherapy.Molecular cancer · 2025Review
- Immune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy.Cellular & molecular immunology · 2025Review
- Radiomics-Based Unsupervised Clustering Identifies Subtypes Associated With Prognosis and Immune Microenvironment in Clear Cell Renal Cell Carcinoma: A Multicenter Study.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide and available therapies, including immunotherapies, are ineffective for many patients. HCC is characterized by intratumoral hypoxia, and increased expression of hypoxia-inducible factor 1α (HIF-1α) in diagnostic biopsies is associated with patient mortality. Here we report the development of 32-134D, a low-molecular-weight compound that effectively inhibits gene expression mediated by HIF-1 and HIF-2 in HCC cells, and blocks human and mouse HCC tumor growth. In immunocompetent mice bearing Hepa1-6 HCC tumors, addition of 32-134D to anti-PD1 therapy increased the rate of tumor eradication from 25% to 67%. Treated mice showed no changes in appearance, behavior, body weight, hemoglobin, or hematocrit. Compound 32-134D altered the expression of a large battery of genes encoding proteins that mediate angiogenesis, glycolytic metabolism, and responses to innate and adaptive immunity. This altered gene expression led to significant changes in the tumor immune microenvironment, including a decreased percentage of tumor-associated macrophages and myeloid-derived suppressor cells, which mediate immune evasion, and an increased percentage of CD8+ T cells and natural killer cells, which mediate antitumor immunity. Taken together, these preclinical findings suggest that combining 32-134D with immune checkpoint blockade may represent a breakthrough therapy for HCC.
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