Orlistat as a FASN inhibitor and multitargeted agent for cancer therapy
Por:
Schcolnik-Cabrera, Alejandro, Chavez-Blanco, Alma, Dominguez-Gomez, Guadalupe, Taja-Chayeb, Lucia, Morales-Barcenas, Rocio, Trejo-Becerril, Catalina, Perez-Cardenas, Enrique, Gonzalez-Fierro, Aurora, Duenas-Gonzalez, Alfonso
Publicada:
1 ene 2018
Resumen:
Introduction: 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. Areas covered: 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. Expert opinion: 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. © 2018 Informa UK Limited, trading as Taylor & Francis Group.
Filiaciones:
Schcolnik-Cabrera, Alejandro:
Inst Nacl Cancerol, Div Basic Res, Mexico City, DF, Mexico
Chavez-Blanco, Alma:
Inst Nacl Cancerol, Div Basic Res, Mexico City, DF, Mexico
Dominguez-Gomez, Guadalupe:
Inst Nacl Cancerol, Div Basic Res, Mexico City, DF, Mexico
Taja-Chayeb, Lucia:
Inst Nacl Cancerol, Div Basic Res, Mexico City, DF, Mexico
Morales-Barcenas, Rocio:
Inst Nacl Cancerol, Div Basic Res, Mexico City, DF, Mexico
Trejo-Becerril, Catalina:
Inst Nacl Cancerol, Div Basic Res, Mexico City, DF, Mexico
Perez-Cardenas, Enrique:
Inst Nacl Cancerol, Div Basic Res, Mexico City, DF, Mexico
Gonzalez-Fierro, Aurora:
Inst Nacl Cancerol, Div Basic Res, Mexico City, DF, Mexico
Duenas-Gonzalez, Alfonso:
Univ Nacl Autonoma Mexico, Inst Nacl Cancerol, Inst Invest Biomed, Unit Biomed Res Canc, Mexico City, DF, Mexico
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