BAPST. A Combo of Common use drugs as metabolic therapy of cancer—a theoretical proposal.

Abstract

: Advances in cancer therapy have yet to impact worldwide cancer mortality. Poor cancer drug affordability is one of the factors limiting mortality burden strikes. Up to now, cancer drug repurposing had no meet expectations concerning drug affordability. The three FDA-approved cancer drugs developed under repurposing -all-trans-retinoic acid, arsenic trioxide, and thalidomide- do not differ in price from other drugs developed under the classical model. Though additional factors affect the whole process from inception to commercialization, the repurposing of widely used, commercially available, and cheap drugs may help. This work reviews the concept of the malignant metabolic phenotype and its exploitation by simultaneously blocking key metabolic processes altered in cancer. We elaborate on a combination called BAPST, which stands for the following drugs and pathways they inhibit: Benserazide (glycolysis), Apomorphine (glutaminolysis), Pantoprazole (Fatty-acid synthesis), Simvastatin (mevalonate pathway), and Trimetazidine (Fatty-acid oxidation). Their respective primary indications are: • Parkinson's disease (benserazide and apomorphine). • Peptic ulcer disease (pantoprazole). • Hypercholesterolemia (simvastatin). • Ischemic heart disease (trimetazidine). When used for their primary indication, the literature review on each of these drugs shows they have a good safety profile and lack predicted pharmacokinetic interaction among them. Most importantly, the inhibitory enzymatic concentrations required for inhibiting their cancer targets enzymes are below the plasma concentrations observed when these drugs are used for their primary indication. Based on that, we propose that the regimen BAPTS merits preclinical testing.