Systematic repurposing screening in xenograft models identifies approved drugs with novel anti-cancer activity

Autor: Saurabh Saha, Kathryn R. Meshaw, Peter C. F. Cheung, Avery S. McMurry, Jeffrey James Roix, S. D. Harrison, Elizabeth Rainbolt
Jazyk: angličtina
Rok vydání: 2014
Předmět:
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
Zdroj: PLoS ONE, Vol 9, Iss 8, p e101708 (2014)
PLoS ONE
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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