ArticleBMC cancer2014
Use of NQO1 status as a selective biomarker for oesophageal squamous cell carcinomas with greater sensitivity to 17-AAG.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 21 citations in OpenAlex.
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- Overcoming acquired resistance to HSP90 inhibition by targeting JAK-STAT signalling in triple-negative breast cancer.BMC cancer · 2019Article
- The germline genetic component of drug sensitivity in cancer cell lines.Nature communications · 2018Article
- A quantile regression forest based method to predict drug response and assess prediction reliability.PloS one · 2018Article
- Bayesian Neural Networks for Selection of Drug Sensitive Genes.Journal of the American Statistical Association · 2018Article
- Azoreductases in drug metabolism.British journal of pharmacology · 2017Review
- A Robust Model-Free Feature Screening Method for Ultrahigh-Dimensional Data.Journal of computational and graphical statistics : a joint publication of American Statistical Association, Institute of Mathematical Statistics, Interface Foundation of North America · 2017Article
- Hsp90 regulates autophagy and plays a role in cancer therapy.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- P-glycoprotein confers acquired resistance to 17-DMAG in lung cancers with an ALK rearrangement.BMC cancer · 2015Article
- High expression of NQO1 is associated with poor prognosis in serous ovarian carcinoma.BMC cancer · 2015Article
- Reversing drug resistance of cisplatin by hsp90 inhibitors in human ovarian cancer cells.International journal of clinical and experimental medicine · 2015Article
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2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOesophageal squamous cell carcinoma (OSCC) is a major health burden in Sub-Saharan Africa, and novel chemotherapies are urgently required to combat this disease. The heat shock protein 90 (HSP90) inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) has previously been proposed as a possible candidate drug. NADPH quinone oxidoreductase 1 (NQO1) is known to increase the potency of 17-AAG, therefore we investigated the effects of 17-AAG in OSCC cell lines in the context of their NQO1 status.
methodsWe used MTT assays to compare the sensitivity of a panel of OSCC cell lines to 17-AAG. Western blotting, and RT-PCR were used to investigate NQO1 protein and mRNA levels, while an RFLP approach was used to investigate the NQO1 C609T SNP.
resultsExpression of NQO1 markedly increased sensitivity to 17-AAG in the OSCC cell lines, while normal fibroblasts, which expressed HSP90 at much lower levels, were more resistant to 17-AAG. In isolation, neither the C609T SNP, nor NQO1 mRNA levels was an accurate predictor of NQO1 protein levels.
conclusionsSince NQO1 greatly enhances the anti-cancer effects of 17-AAG, this could be used as a selective marker for patients that would benefit most from 17-AAG chemotherapy at low doses. Testing for the presence of the C609T SNP in both alleles could be used as a screen to exclude potentially poor responders to 17-AAG treatment at low dosages.
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