Call for Papers  

Article Details

Review Article

PaSTe. Blockade of the Lipid Phenotype of Prostate Cancer as Metabolic Therapy: A Theoretical Proposal


Adriana Romo-Perez, Guadalupe Domínguez-Gómez, Alma Chávez-Blanco, Aurora González-Fierro, José Correa-Basurto and Alfonso Dueñas-González*   Pages 1 - 21 ( 21 )


Background: Prostate cancer is the most frequently diagnosed malignancy in 112 countries and is the leading cause of death in eighteen. In addition to continuing research on prevention and early diagnosis, improving treatments and making them more affordable is imperative. In this sense, the therapeutic repurposing of low-cost and widely available drugs could reduce global mortality from this disease. The malignant metabolic phenotype is becoming increasingly important due to its therapeutic implications. Cancer generally is characterized by hyperactivation of glycolysis, glutaminolysis, and fatty acid synthesis. However, prostate cancer is particularly lipidic; it exhibits increased activity in the pathways for synthesizing fatty acids, cholesterol, and fatty acid oxidation (FAO).

Objective: Based on a literature review, we propose the PaSTe regimen (Pantoprazole, Simvastatin, Trimetazidine) as a metabolic therapy for prostate cancer. Pantoprazole and simvastatin inhibit the enzymes fatty acid synthase (FASN) and 3-hydroxy-3-methylglutaryl- coenzyme A reductase (HMGCR), therefore, blocking the synthesis of fatty acids and cholesterol, respectively. In contrast, trimetazidine inhibits the enzyme 3-β-Ketoacyl- CoA thiolase (3-KAT), an enzyme that catalyzes the oxidation of fatty acids (FAO). It is known that the pharmacological or genetic depletion of any of these enzymes has antitumor effects in prostatic cancer.

Results: Based on this information, we hypothesize that the PaSTe regimen will have increased antitumor effects and may impede the metabolic reprogramming shift. Existing knowledge shows that enzyme inhibition occurs at molar concentrations achieved in plasma at standard doses of these drugs.

Conclusion: We conclude that this regimen deserves to be preclinically evaluated because of its clinical potential for the treatment of prostate cancer.


Prostate cancer, metabolic blockade, cancer drug repurposing, de novo fatty-acid synthesis, mevalonate pathway, fatty-acid oxidation.


Read Full-Text article