ArticleProceedings of the National Academy of Sciences of the United States of America2014
Repurposing of bisphosphonates for the prevention and therapy of nonsmall cell lung and breast cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Bisphosphonates and risk of cancers: a systematic review and meta-analysis.British journal of cancer · 2020Pooled it
- Review
- Article
- Article
- Structural insights into the binding of zoledronic acid with RANKLFrontiers in molecular biosciences · 2022Article
- Cholesterol synthesis disruption combined with a molecule-targeted drug is a promising metabolic therapy for EGFR mutant non-small cell lung cancer.Translational lung cancer research · 2021Article
- Beyond bone biology: Lessons from team science.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2020Article
- Next Generation Lipophilic Bisphosphonate Shows Antitumor Effect in Colorectal Cancer In Vitro and In Vivo.Pathology oncology research : POR · 2020Article
- Bisphosphonates Zometa and Fosamax Synergize with Metformin to Prevent AOM-Induced Colon Cancer in F344 Rat Model.Cancer prevention research (Philadelphia, Pa.) · 2020Article
- Retrospective study on the efficacy of bisphosphonates in tyrosine kinase inhibitor-treated patients with non-small cell lung cancer exhibiting bone metastasis.Oncology letters · 2019Article
- Current state and outlook for drug repositioning anticipated in the field of ovarian cancer.Journal of gynecologic oncology · 2019Review
- Regulation of Skeletal Homeostasis.Endocrine reviews · 2018Review
- Bisphosphonate-Generated ATP-Analogs Inhibit Cell Signaling Pathways.Journal of the American Chemical Society · 2018Article
- Oral bisphosphonate use and lung cancer incidence among postmenopausal women.Annals of oncology : official journal of the European Society for Medical Oncology · 2018Article
- In Silico-Based Repositioning of Phosphinothricin as a Novel Technetium-99m Imaging Probe with Potential Anti-Cancer Activity.Molecules (Basel, Switzerland) · 2018Article
- FSIP1 binds HER2 directly to regulate breast cancer growth and invasiveness.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Anticancer Activity of Polyoxometalate-Bisphosphonate Complexes: Synthesis, Characterization, In Vitro and In Vivo Results.Inorganic chemistry · 2017Article
- BRCA1 haploinsufficiency cell-autonomously activates RANKL expression and generates denosumab-responsive breast cancer-initiating cells.Oncotarget · 2017Article
- Targeting Cancer Cells with a Bisphosphonate Prodrug.ChemMedChem · 2016Article
- KRAS-mutation status dependent effect of zoledronic acid in human non-small cell cancer preclinical models.Oncotarget · 2016Article
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28 authors at 5 institutions in 4 countries.
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Abstract
A variety of human cancers, including nonsmall cell lung (NSCLC), breast, and colon cancers, are driven by the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases. Having shown that bisphosphonates, a class of drugs used widely for the therapy of osteoporosis and metastatic bone disease, reduce cancer cell viability by targeting HER1, we explored their potential utility in the prevention and therapy of HER-driven cancers. We show that bisphosphonates inhibit colony formation by HER1(ΔE746-A750)-driven HCC827 NSCLCs and HER1(wt)-expressing MB231 triple negative breast cancers, but not by HER(low)-SW620 colon cancers. In parallel, oral gavage with bisphosphonates of mice xenografted with HCC827 or MB231 cells led to a significant reduction in tumor volume in both treatment and prevention protocols. This result was not seen with mice harboring HER(low) SW620 xenografts. We next explored whether bisphosphonates can serve as adjunctive therapies to tyrosine kinase inhibitors (TKIs), namely gefitinib and erlotinib, and whether the drugs can target TKI-resistant NSCLCs. In silico docking, together with molecular dynamics and anisotropic network modeling, showed that bisphosphonates bind to TKIs within the HER1 kinase domain. As predicted from this combinatorial binding, bisphosphonates enhanced the effects of TKIs in reducing cell viability and driving tumor regression in mice. Impressively, the drugs also overcame erlotinib resistance acquired through the gatekeeper mutation T790M, thus offering an option for TKI-resistant NSCLCs. We suggest that bisphosphonates can potentially be repurposed for the prevention and adjunctive therapy of HER1-driven cancers.
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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.