Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Mexico City, Mexico.
Curr Mol Pharmacol. 2022;15(6):815-831. doi: 10.2174/1874467214666211006123728.
Cancer therapy advances have yet to impact global cancer mortality. One of the factors limiting mortality burden reduction is the high cost of cancer drugs. Cancer drug repurposing has already failed to meet expectations in terms of 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 that they have a good safety profile and lack predicted pharmacokinetic interaction among them. Based on that, we propose that the BAPST regimen merits preclinical testing.
癌症治疗的进展尚未对全球癌症死亡率产生影响。限制死亡率负担降低的因素之一是癌症药物的高成本。癌症药物再利用在药物可负担性方面已经未能达到预期。根据再利用开发的三种获得美国食品和药物管理局批准的癌症药物：全反式维甲酸、三氧化二砷和沙利度胺，其价格与根据经典模型开发的其他药物没有区别。尽管其他因素会影响从概念到商业化的整个过程，但广泛使用、可商购和廉价药物的再利用可能会有所帮助。这项工作回顾了恶性代谢表型的概念及其通过同时阻断癌症中改变的关键代谢过程的利用。我们详细介绍了一种称为 BAPST 的组合，它代表了以下药物及其抑制的途径：苄丝肼（糖酵解）、阿朴吗啡（谷氨酰胺分解）、泮托拉唑（脂肪酸合成）、辛伐他汀（甲羟戊酸途径）和曲美他嗪（脂肪酸氧化）。它们各自的主要适应症是：•帕金森病（苄丝肼和阿朴吗啡）。•消化性溃疡病（泮托拉唑）。•高胆固醇血症（辛伐他汀）。•缺血性心脏病（曲美他嗪）。当用于其主要适应症时，对这些药物中的每一种的文献综述都表明它们具有良好的安全性，并且彼此之间缺乏预测的药代动力学相互作用。基于此，我们提出 BAPST 方案值得进行临床前测试。
