1. Systematic repurposing screening in xenograft models identifies approved drugs with novel anti-cancer activity
- Author
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Saurabh Saha, Kathryn R. Meshaw, Peter C. F. Cheung, Avery S. McMurry, Jeffrey James Roix, S. D. Harrison, and Elizabeth Rainbolt
- Subjects
Male ,Melanomas ,Skin Neoplasms ,Cancer Treatment ,Tetrazoles ,lcsh:Medicine ,Pharmacology ,Biochemistry ,Mice ,Neoplasms ,Drug Discovery ,Basic Cancer Research ,Medicine and Health Sciences ,lcsh:Science ,Drug Approval ,Skin Tumors ,Neurological Tumors ,Repurposing ,Multidisciplinary ,Drug discovery ,Etidronic Acid ,Dacarbazine ,Drug repositioning ,Neurology ,Oncology ,Female ,Risedronic Acid ,Research Article ,Biotechnology ,medicine.drug ,Drug Research and Development ,Mice, Nude ,Antineoplastic Agents ,Mice, Transgenic ,Dermatology ,Cell Line, Tumor ,Temozolomide ,medicine ,Animals ,Humans ,Medical prescription ,business.industry ,Biphenyl Compounds ,lcsh:R ,Drug Repositioning ,Biology and Life Sciences ,Cancers and Neoplasms ,Cancer ,medicine.disease ,Xenograft Model Antitumor Assays ,High-Throughput Screening Assays ,Mice, Inbred C57BL ,Clinical trial ,Thalidomide ,Benzimidazoles ,lcsh:Q ,Clinical Medicine ,business ,Glioblastoma Multiforme - Abstract
Approved drugs target approximately 400 different mechanisms of action, of which as few as 60 are currently used as anti-cancer therapies. Given that on average it takes 10–15 years for a new cancer therapeutic to be approved, and the recent success of drug repurposing for agents such as thalidomide, we hypothesized that effective, safe cancer treatments may be found by testing approved drugs in new therapeutic settings. Here, we report in-vivo testing of a broad compound collection in cancer xenograft models. Using 182 compounds that target 125 unique target mechanisms, we identified 3 drugs that displayed reproducible activity in combination with the chemotherapeutic temozolomide. Candidate drugs appear effective at dose equivalents that exceed current prescription levels, suggesting that additional pre-clinical efforts will be needed before these drugs can be tested for efficacy in clinical trials. In total, we suggest drug repurposing is a relatively resource-intensive method that can identify approved medicines with a narrow margin of anti-cancer activity.
- Published
- 2014