Orlistat as a FASN inhibitor and multitargeted agent for cancer therapy
| Autor: | Rocio Morales-Barcenas, Alma Chavez-Blanco, Lucia Taja-Chayeb, Enrique Pérez-Cárdenas, Guadalupe Domínguez-Gómez, Aurora Gonzalez-Fierro, Alfonso Dueñas-González, Alejandro Schcolnik-Cabrera, Catalina Trejo-Becerril |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer therapy Antineoplastic Agents Lactones 03 medical and health sciences 0302 clinical medicine Neoplasms medicine Animals Humans Pharmacology (medical) Molecular Targeted Therapy Enzyme Inhibitors Orlistat Pharmacology chemistry.chemical_classification Glutaminolysis Drug Repositioning Fatty acid General Medicine Fatty Acid Synthase Type I Drug repositioning 030104 developmental biology Enzyme chemistry Drug Design 030220 oncology & carcinogenesis Lipogenesis Cancer cell Cancer research Administration Intravenous medicine.drug |
| Zdroj: | Expert Opinion on Investigational Drugs. 27:475-489 |
| ISSN: | 1744-7658 1354-3784 |
| DOI: | 10.1080/13543784.2018.1471132 |
| Popis: | Cancer cells have increased glycolysis and glutaminolysis. Their third feature is increased de novo lipogenesis. As such, fatty acid (FA) synthesis enzymes are over-expressed in cancer and their depletion causes antitumor effects. As fatty acid synthase (FASN) plays a pivotal role in this process, it is an attractive target for cancer therapy.This is a review of the lipogenic phenotype of cancer and how this phenomenon can be exploited for cancer therapy using inhibitors of FASN, with particular emphasis on orlistat as a repurposing drug.Disease stabilization only has been observed with a highly selective FASN inhibitor used as a single agent in clinical trials. It is too early to say whether the absence of tumor responses other than stabilization results because even full inhibition of FASN is not enough to elicit antitumor responses. The FASN inhibitor orlistat is a 'dirty' drug with target-off actions upon at least seven targets with a proven role in tumor biology. The development of orlistat formulations suited for its intravenous administration is a step ahead to shed light on the concept that drug promiscuity can or not be a virtue. |
| Databáze: | OpenAIRE |
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