ArticleBritish journal of pharmacology2014
Hypoxia modulates the activity of a series of clinically approved tyrosine kinase inhibitors.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 33 citations in OpenAlex.
- FDX1 Regulates the Phosphorylation of ATM, DNA-PKcs Akt, and EGFR and Affects Radioresistance Under Severe Hypoxia in the Glioblastoma Cell Line T98G.International journal of molecular sciences · 2025Article
- Assessing MTT and sulforhodamine B cell proliferation assays under multiple oxygen environments.Cytotechnology · 2023Article
- Low-Cost, High-Pressure-Synthesized Oxygen-Entrapping Materials to Improve Treatment of Solid Tumors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Review
- Systematic alteration of in vitro metabolic environments reveals empirical growth relationships in cancer cell phenotypes.Cell reports · 2021Article
- Kinomic profile in patient-derived glioma cells during hypoxia reveals c-MET-PI3K dependency for adaptation.Theranostics · 2021Article
- HIF and COX-2 expression in triple negative breast cancer cells with hypoxia and 5-fluorouracil.Current cancer reports · 2020Article
- Normoxic Tumour Extracellular Vesicles Modulate the Response of Hypoxic Cancer and Stromal Cells to Doxorubicin In Vitro.International journal of molecular sciences · 2020Article
- High-Throughput Flow Cytometry Identifies Small-Molecule Inhibitors for Drug Repurposing in T-ALL.SLAS discovery : advancing life sciences R & D · 2018Article
- Intravital Imaging to Monitor Therapeutic Response in Moving Hypoxic Regions Resistant to PI3K Pathway Targeting in Pancreatic Cancer.Cell reports · 2018Article
- The effects of triptolide on the pharmacokinetics of sorafenib in rats and its potential mechanism.Pharmaceutical biology · 2017Article
- Bis(thiosemicarbazone) Complexes of Cobalt(III). Synthesis, Characterization, and Anticancer Potential.Inorganic chemistry · 2017Article
- Hypoxia Mediates Differential Response to Anti-EGFR Therapy in HNSCC Cells.International journal of molecular sciences · 2017Article
- Switching off malignant mesothelioma: exploiting the hypoxic microenvironment.Genes & cancer · 2016Review
- Targeting the hypoxic fraction of tumours using hypoxia-activated prodrugs.Cancer chemotherapy and pharmacology · 2016Review
- Cell Death Conversion under Hypoxic Condition in Tumor Development and Therapy.International journal of molecular sciences · 2015Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeHypoxia in tumours is known to cause resistance to conventional chemotherapeutic drugs. In contrast, little is known about the effects of hypoxia on targeted anti-cancer drugs. This study evaluated the effect of hypoxia on a series of clinically approved tyrosine kinase inhibitors (TKIs). EXPERIMENTAL APPROACH: The effect of hypoxia (0.1% oxygen) on the activity of conventional cytotoxic drugs (5-fluorouracil, doxorubicin and vinblastine), the hypoxia-activated prodrug tirapazamine and 9 TKIs was determined in a panel of cell lines. Where hypoxia had a marked effect on chemosensitivity, Western blot analysis was conducted to determine the effect of hypoxia on target expression and the effect of TKIs on cell signalling response under aerobic and hypoxic conditions. KEY
resultsThree patterns of chemosensitivity were observed: resistance under hypoxia, equitoxic activity against hypoxic and aerobic cells, and preferential cytotoxicity to hypoxic cells. Significant hypoxia selectivity (independent of HIF1) was observed in the case of dasatinib and this correlated with the ability of dasatinib to inhibit phosphorylation of Src at tyrosine 530. Sorafenib was significantly less effective under hypoxic conditions but resistance did not correlate with hypoxia-induced changes in Raf/MEK/ERK signalling. CONCLUSIONS AND IMPLICATIONS: Hypoxia influences the activity of TKIs but in contrast to conventional cytotoxic drugs, preferential activity against hypoxic cells can occur. The search for hypoxia-targeted therapies has been long and fruitless and this study suggests that some clinically approved TKIs could preferentially target the hypoxic fraction of some tumour types.
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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.