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      Repurposing old drugs in oncology: Opportunities with clinical and regulatory challenges ahead

      1 , 2
      Journal of Clinical Pharmacy and Therapeutics
      Wiley

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          Abstract

          In order to expedite the availability of drugs to treat cancers in a cost-effective manner, repurposing of old drugs for oncological indications is gathering momentum. Revolutionary advances in pharmacology and genomics have demonstrated many old drugs to have activity at novel antioncogenic pharmacological targets. We decided to investigate whether prospective studies support the promises of nonclinical and retrospective clinical studies on repurposing three old drugs, namely metformin, valproate and astemizole.

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          Most cited references3

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          A screen of approved drugs and molecular probes identifies therapeutics with anti-Ebola virus activity.

          Currently, no approved therapeutics exist to treat or prevent infections induced by Ebola viruses, and recent events have demonstrated an urgent need for rapid discovery of new treatments. Repurposing approved drugs for emerging infections remains a critical resource for potential antiviral therapies. We tested ~2600 approved drugs and molecular probes in an in vitro infection assay using the type species, Zaire ebolavirus. Selective antiviral activity was found for 80 U.S. Food and Drug Administration-approved drugs spanning multiple mechanistic classes, including selective estrogen receptor modulators, antihistamines, calcium channel blockers, and antidepressants. Results using an in vivo murine Ebola virus infection model confirmed the protective ability of several drugs, such as bepridil and sertraline. Viral entry assays indicated that most of these antiviral drugs block a late stage of viral entry. By nature of their approved status, these drugs have the potential to be rapidly advanced to clinical settings and used as therapeutic countermeasures for Ebola virus infections.
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            Statins and cancer: A systematic review and meta-analysis.

            Systematic reviews on the association between statin therapy and cancer have focused on randomised trials without assessing the quality of evidence. We aimed to review the overall evidence taking study quality into consideration. Publications of original studies on the effect of statin treatment on cancer in adult patients were searched on MEDLINE, EMBASE and CENTRAL databases upto October 2007. Our search yielded 37 eligible original studies out of 3607 references. Five studies were additionally found through manual search. Thus, 42 studies were included in the analyses: 17 randomised controlled trials, 10 cohort studies, and 15 case-control studies. Statins had no effect on the overall incidence of cancer (median risk ratio (RR) 0.96, range 0.72 to 1.2), or on the incidence of lung (median RR 0.92, range 0.83 to 3.0), breast (median RR 1.04, range 0.74 to 19) or prostate cancer (median RR 0.96, range 0.33 to 1.7). They seemed to protect from stomach (median RR 0.59, range 0.40 to 0.88) and liver cancer (median RR 0.62, range 0.33 to 1.2), and from lymphoma (median RR 0.74, range 0.28 to 2.2). They increased the incidence of both melanoma (median RR 1.5, range 1.3 to 1.7) and non-melanoma skin cancer (median RR 1.6, range 1.2 to 2.2). The effect varied, yet inconsistently, by statin type. The median follow-up time was 4 years. The strength of evidence was mostly weak. The evidence suggests that statins do not have short-term effects on cancer risk. The evidence on potentially protective or harmful effects is inconclusive. High quality cohort studies with long follow-up are needed to resolve the issue.
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              Inventing new therapies without reinventing the wheel: the power of drug repurposing.

              This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                Journal of Clinical Pharmacy and Therapeutics
                J Clin Pharm Ther
                Wiley
                02694727
                February 2019
                February 2019
                September 15 2018
                : 44
                : 1
                : 6-22
                Affiliations
                [1 ]Pharmaceutical Consultant; Gerrards Cross Buckinghamshire UK
                [2 ]Department of Pharmaceutical Medicine; School of Cancer and Pharmaceutical Sciences; Faculty of Life Sciences and Medicine; King's College; London UK
                Article
                10.1111/jcpt.12759
                30218625
                91042ef9-73ae-4df9-9aca-969cbb006f58
                © 2018

                http://doi.wiley.com/10.1002/tdm_license_1.1

                http://onlinelibrary.wiley.com/termsAndConditions#vor

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