New Australian study below.
"Following the completion of the primary screening assay, 33 drugs were identified from an FDA approved drug library that either inhibited migration or were cytotoxic to the PC-3 cells. Based on the data obtained from the subsequent validation studies, mitoxantrone hydrochloride, simvastatin, fluvastatin and vandetanib were identified as strong candidates that can inhibit both the migration and invasion of PC-3 cells without significantly affecting cell viability."
"mitoxantrone hydrochloride"? From Wikipedia: "The combination of mitoxantrone and prednisone is approved as a second-line treatment for metastatic hormone-refractory prostate cancer."
"simvastatin" was the statin I chose 6-7 years ago; specifically for PCa ("fluvastatin" wasn't in the running). Too bad the 80 mg dose had just been withdrawn from the U.S. market. (The FDA does allow grandfathering, but I had delayed too long.) Not all statins are equal in the PCa literature, & dose matters.
"vandetanib"? There has been a Phase II Canadian trial with bicalutamide. "The combination of vandetanib and bicalutamide was associated with considerable toxicity and did not have superior efficacy over bicalutamide alone." ncbi.nlm.nih.gov/pubmed/246...
The absence of Metformin as a repurposing candidate is odd: "Metformin significantly inhibited PC-3 cell proliferation, migration, and invasion." ncbi.nlm.nih.gov/pubmed/258... Exactly what they were looking for.
-Patrick
ncbi.nlm.nih.gov/pubmed/269...
Clin Exp Metastasis. 2016 Mar 1. [Epub ahead of print]
Repositioning "old" drugs for new causes: identifying new inhibitors of prostate cancer cell migration and invasion.
Shah ET1,2, Upadhyaya A1,2, Philp LK1,2, Tang T1, Skalamera D3,2, Gunter J1,2, Nelson CC1,2, Williams ED1,2, Hollier BG4,5.
Author information
1Australian Prostate Cancer Research Centre-Queensland, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
2Translational Research Institute, Brisbane, Australia.
3The University of Queensland Diamantina Institute, University of Queensland, Brisbane, Australia.
4Australian Prostate Cancer Research Centre-Queensland, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. b.hollier@qut.edu.au.
5Translational Research Institute, Brisbane, Australia. b.hollier@qut.edu.au.
Abstract
The majority of prostate cancer (PCa) deaths occur due to the metastatic spread of tumor cells to distant organs. Currently, there is a lack of effective therapies once tumor cells have spread outside the prostate. It is therefore imperative to rapidly develop therapeutics to inhibit the metastatic spread of tumor cells. Gain of cell motility and invasive properties is the first step of metastasis and by inhibiting motility one can potentially inhibit metastasis. Using the drug repositioning strategy, we developed a cell-based multi-parameter primary screening assay to identify drugs that inhibit the migratory and invasive properties of metastatic PC-3 PCa cells. Following the completion of the primary screening assay, 33 drugs were identified from an FDA approved drug library that either inhibited migration or were cytotoxic to the PC-3 cells. Based on the data obtained from the subsequent validation studies, mitoxantrone hydrochloride, simvastatin, fluvastatin and vandetanib were identified as strong candidates that can inhibit both the migration and invasion of PC-3 cells without significantly affecting cell viability. By employing the drug repositioning strategy instead of a de novo drug discovery and development strategy, the identified drug candidates have the potential to be rapidly translated into the clinic for the management of men with aggressive forms of PCa.
KEYWORDS:
Drug repositioning; IncuCyte™; Migration; PC-3; Prostate cancer; Scratch wound assay
PMID: 26932199 [PubMed - as supplied by publisher]
