ArticleInternational journal of cancer2013
Overcoming evasive resistance from vascular endothelial growth factor a inhibition in sarcomas by genetic or pharmacologic targeting of hypoxia-inducible factor 1α.
Article in International journal of cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Phase Ib/II Study of the Safety and Efficacy of Combination Therapy with Multikinase VEGF Inhibitor Pazopanib and MEK Inhibitor Trametinib In Advanced Soft Tissue Sarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- Review
- Ionising radiation exposure-induced regulation of selected biomarkers and their impact in cancer and treatment.Frontiers in nuclear medicine · 2024Review
- Metronomic chemotherapy in cancer treatment: new wine in an old bottle.Theranostics · 2024Review
- Article
- Sarcoma treatment in the era of molecular medicine.EMBO molecular medicine · 2020Review
- Bevacizumab promotes active biological behaviors of human umbilical vein endothelial cells by activating TGFβ1 pathwaysCancer biology & medicine · 2020Article
- Revascularization after angiogenesis inhibition favors new sprouting over abandoned vessel reuse.Angiogenesis · 2019Article
- Discontinuous Schedule of Bevacizumab in Colorectal Cancer Induces Accelerated Tumor Growth and Phenotypic Changes.Translational oncology · 2018Article
- Conditioning neoadjuvant therapies for improved immunotherapy of cancer.Biochemical pharmacology · 2017Review
- [Hypoxia-inducible factor-1α and CD133 predicts pathological complete response and survival for locally advanced rectal cancer patients after neoadjuvant chemoradiotherapy].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2017Article
- A prognostic profile of hypoxia-induced genes for localised high-grade soft tissue sarcoma.British journal of cancer · 2016Article
- Article
- Inhibition of carbonic anhydrase potentiates bevacizumab treatment in cholangiocarcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Overcoming Hypoxia-Mediated Tumor Progression: Combinatorial Approaches Targeting pH Regulation, Angiogenesis and Immune Dysfunction.Frontiers in cell and developmental biology · 2016Review
- Hypoxia-activated chemotherapeutic TH-302 enhances the effects of VEGF-A inhibition and radiation on sarcomas.British journal of cancer · 2015Article
- RETRACTED: Inhibition of vascular endothelial growth factor A and hypoxia-inducible factor 1α maximizes the effects of radiation in sarcoma mouse models through destruction of tumor vasculature.International journal of radiation oncology, biology, physics · 2015Article
- Metronomics: towards personalized chemotherapy?Nature reviews. Clinical oncology · 2014Review
- Hypoxia-dependent modification of collagen networks promotes sarcoma metastasis.Cancer discovery · 2013Article
- Chronic inhibition of tumor cell-derived VEGF enhances the malignant phenotype of colorectal cancer cells.BMC cancer · 2013Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Increased levels of hypoxia and hypoxia-inducible factor 1α (HIF-1α) in human sarcomas correlate with tumor progression and radiation resistance. Prolonged antiangiogenic therapy of tumors not only delays tumor growth but may also increase hypoxia and HIF-1α activity. In our recent clinical trial, treatment with the vascular endothelial growth factor A (VEGF-A) antibody, bevacizumab, followed by a combination of bevacizumab and radiation led to near complete necrosis in nearly half of sarcomas. Gene Set Enrichment Analysis of microarrays from pretreatment biopsies found that the Gene Ontology category "Response to hypoxia" was upregulated in poor responders and that the hierarchical clustering based on 140 hypoxia-responsive genes reliably separated poor responders from good responders. The most commonly used chemotherapeutic drug for sarcomas, doxorubicin (Dox), was recently found to block HIF-1α binding to DNA at low metronomic doses. In four sarcoma cell lines, HIF-1α shRNA or Dox at low concentrations blocked HIF-1α induction of VEGF-A by 84-97% and carbonic anhydrase 9 by 83-93%. HT1080 sarcoma xenografts had increased hypoxia and/or HIF-1α activity with increasing tumor size and with anti-VEGF receptor antibody (DC101) treatment. Combining DC101 with HIF-1α shRNA or metronomic Dox had a synergistic effect in suppressing growth of HT1080 xenografts, at least in part via induction of tumor endothelial cell apoptosis. In conclusion, sarcomas respond to increased hypoxia by expressing HIF-1α target genes that may promote resistance to antiangiogenic and other therapies. HIF-1α inhibition blocks this evasive resistance and augments destruction of the tumor vasculature.
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