ArticleMolecular cancer therapeutics2011
The novel Bcl-2 inhibitor ABT-737 is more effective in hypoxia and is able to reverse hypoxia-induced drug resistance in neuroblastoma cells.
Article in Molecular cancer therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Advances in Targeting Growth Factor Signalling in Neuroblastoma and Overcoming Drug Resistance.Cells · 2025Review
- Hallmarks of cancer resistance.iScience · 2024Review
- Synergistic cytotoxicity of perifosine and ABT-737 to colon cancer cells.Journal of cellular and molecular medicine · 2023Article
- The antihyperlipidemic equivalent combinatorial components from peel of Citrus reticulata 'Chachi'.Journal of food and drug analysis · 2022Article
- Bcl-2/Bcl-xL inhibitor ABT-263 overcomes hypoxia-driven radioresistence and improves radiotherapy.Cell death & disease · 2021Article
- A direct comparison of selective BH3-mimetics reveals BCL-XBritish journal of cancer · 2020Article
- Article
- Influence of hypoxia-related genetic polymorphisms on the prognosis of patients with metastatic gastric cancer treated with EOF.Oncology letters · 2018Article
- Pro-survival responses to the dual inhibition of anti-apoptotic Bcl-2 family proteins and mTOR-mediated signaling in hypoxic colorectal carcinoma cells.BMC cancer · 2016Article
- Oncolytic viral therapy for neuroblastoma cells with Sindbis virus AR339 strain.Pediatric surgery international · 2015Article
- Rapamycin rescues ABT-737 efficacy in small cell lung cancer.Cancer research · 2014Article
- BMX acts downstream of PI3K to promote colorectal cancer cell survival and pathway inhibition sensitizes to the BH3 mimetic ABT-737.Neoplasia (New York, N.Y.) · 2014Article
- Hypoxia modulates the activity of a series of clinically approved tyrosine kinase inhibitors.British journal of pharmacology · 2014Article
- Characterization of neuroblastoma bone invasion/metastasis in established bone metastatic model of SY5Y and KCNR cell lines.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2013Article
- Hypoxia-induced cytotoxic drug resistance in osteosarcoma is independent of HIF-1Alpha.PloS one · 2013Article
- Anti-cancer drug discovery and development: Bcl-2 family small molecule inhibitors.Communicative & integrative biology · 2012Article
- Understanding sensitivity to BH3 mimetics: ABT-737 as a case study to foresee the complexities of personalized medicine.Journal of molecular signaling · 2012Article
- Acidosis promotes Bcl-2 family-mediated evasion of apoptosis: involvement of acid-sensing G protein-coupled receptor Gpr65 signaling to Mek/Erk.The Journal of biological chemistry · 2012Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Neuroblastoma is a common solid tumor of childhood and advanced disease carries a poor prognosis despite intensive multimodality therapy. Hypoxia is a common feature of solid tumors because of poorly organized tumor-induced neovasculature. Hypoxia is associated with advanced stage and poor outcome in a range of tumor types, and leads to resistance to clinically relevant cytotoxic agents in neuroblastoma and other pediatric tumors in vitro. Resistance to apoptosis is a common feature of tumor cells and leads to pleiotropic drug resistance, mediated by Bcl-2 family proteins. ABT-737 is a novel small-molecule inhibitor of Bcl-2 and Bcl-x(L) that is able to induce apoptosis in a range of tumor types. Neuroblastoma cell lines are relatively resistant to ABT-737-induced apoptosis in normoxia, but in contrast to the situation with conventional cytotoxic agents are more sensitive in hypoxia. This sensitization is because of an increase in ABT-737-induced apoptosis and is variably dependent upon the presence of functional hypoxia-inducible factor 1 (HIF-1) α. In contrast to the situation in colon carcinoma and non-small cell lung cancer cells, hypoxia does not result in downregulation of the known ABT-737 resistance factor, Mcl-1, nor any other Bcl-2 family proteins. ABT-737 sensitizes neuroblastoma cells to clinically relevant cytotoxic agents under normal levels of oxygen, and importantly, this sensitization is maintained under hypoxia when neuroblastoma cells are resistant to these agents. Thus rational combinations of ABT-737 and conventional cytotoxics offer a novel approach to overcoming hypoxia-induced drug resistance in neuroblastoma.
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