By Ashraf-Uz-Zaman, Md, Sanaullah Sajib, Md, Cucullo, Luca, Mikelis, Constantinos M., German, Nadezhda A
Abstract:
Several recent reports have highlighted the feasibility of the use of penfluridol, a well-known antipsychotic agent, as a chemotherapeutic agent. In vivo experiments have confirmed the cytotoxic activity of penfluridol in triple-negative breast cancer model, lung cancer model, and further studies have been proposed to assess its anticancer activity and viability for the treatment of glioblastomas. However, penfluridol anticancer activity was observed at a dosage significantly higher than that administered in antipsychotic therapy, thus raising the concern for the potential onset of CNS side effects in patients undergoing intensive pharmacological treatment. In this study, we evaluate the potential CNS toxicity of penfluridol side by side with a set of analogs.
Traditionally, de novo drug discovery for cancer treatment is invariably associated with high cost for preclinical and clinical studies which is estimated at approximately 1.042 billion dollars per drug1.
Therefore, repurposing approved drugs to extend their therapeutic viability to other diseases (such as cancer treatment) is likely to afford the quickest and most cost-effective transition from bench to bedside2,3. At the same time, to avoid potential side toxicity issues, it is crucial to gather all available toxicological information associated with the use of a given drug4 and prevent scenarios similar to bevacizumab, cetuximab and others5, the USA Food and Drug Administration (FDA) developed guidance for a systemic approach to collect and report compound-associated toxicities6.This is especially important when the proposed dosage and/or frequency of administration of a repurposed drug are substantially different, (higher) than those previously associated for its original therapeutic scope.
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