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HIF Inhibitors: Status of Current Clinical Development
Abstract
Purpose of review In this review, the importance of the hypoxia inducible factor (HIF) pathway in tumorigenesis and cancer treatment outcomes will be discussed. The outcomes of phase II and III clinical trials of direct HIF inhibitors in the treatment of cancer will be reviewed.Recent findings The HIF signaling pathway is activated by tumor-induced hypoxia or by inactivating mutations of the VHL gene. HIF is a transcription factor which regulates the expression of genes involved in adjusting mechanisms to hypoxia such as angiogenesis or apoptosis as well as tumor growth, invasion, and metastasis. The HIF pathway has a key role in development of resistance to different treatment modalities and higher expression of the HIF molecule is associated with poor prognosis. Clinical studies of the HIF inhibitors in patients with advanced/refractory cancers suggest benefit and warrant further studies of the HIF inhibitors either as a single agent or in combination with other therapeutic agents.
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“HIF inhibitors are under pre-clinical investigation and clinical trials”
From HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells (2021) · cites this paper as [9]
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“Clinical studies of HIF inhibitors indicate benefit and justify further evaluation either as a single agent or in combination with other antitumor agents (6).”
From Cross-talk between HIF and PD-1/PD-L1 pathways in carcinogenesis and therapy (2022) · cites this paper as [6]
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Metadata
- Authors
- Fallah, J., & Rini, B. I.
- Affiliations
- Cleveland Clinic (US)
- Corresponding author
- Rini, Brian I.
- Venue
- Current Oncology Reports
- Published
- 2019-01
- Volume
- 21
- Issue
- 1
- Pages
- 6-6
- ISSN
- 1523-3790 (ISSN-L)
- 1534-6269
- OpenAlex
- W2913218828
- Cited by
- 308
- References
- 62
- Citations by year
- 2026: 10 · 2025: 20 · 2024: 43 · 2023: 52 · 2022: 68 · 2021: 64 · 2020: 45 · 2019: 5
- FWCI
- 4.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Current Oncology Reports (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Keywords
- hypoxia-inducible factor, HIF inhibitors, tumor hypoxia, VHL mutation, angiogenesis, apoptosis, metastasis, treatment resistance, advanced cancer, clinical trials, combination therapy
- MeSH terms
- Antineoplastic Agents, Carcinoma, Renal Cell, Clinical Trials as Topic, Humans, Kidney Neoplasms, Prognosis, Research Design, Hypoxia-Inducible Factor 1, alpha Subunit
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