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

WHAT IS KNOWN AND OBJECTIVE: 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. METHODS: We conducted an extensive literature search through PubMed to gather representative nonclinical and retrospective clinical studies that investigated the potential repurposing of these three drugs for oncological indications. We then searched for prospective studies aimed at confirming the promises of retrospective data. RESULTS AND DISCUSSION: While evidence from nonclinical and retrospective clinical studies with these drugs appears highly promising, large scale prospective studies are either lacking or have failed to substantiate this promise. We provide a brief discussion of some of the challenges in repurposing. Principal challenges and obstacles relate to heterogeneity of cancers studied without considering their molecular signatures, trials with small sample size and short duration, failure consider issues of ethnicity of study population and effective antioncogenic doses of the drug studied. WHAT IS NEW AND CONCLUSION: Well-designed prospective studies demonstrating efficacy are required for repurposing old drugs for oncology indications, just as they are for new chemical entities for any indication. Early and ongoing interactions with regulatory authorities are invaluable. We outline a tentative framework for a structured approach to repurposing old drugs for novel indications in oncology.