title: Chronic mechanistic target of rapamycin inhibition: preventing cancer to delay aging, or vice versa?.
abstract: Cancer and aging appear to be inexorably linked, yet approaches to ameliorate them in concert are lacking. Although not (easily) feasible in humans, years of preclinical research show that diet and growth factor restriction each successfully address cancer and aging together. Chronic treatment of genetically heterogeneous mice with an enteric formulation of rapamycin (eRapa) extended maximum lifespan of both genders when started in mid or late life. In part, cancer amelioration in treated mice suggested that long-term eRapa, like diet restriction, could be a pharmacological approach feasible for use in the clinic. We review the current understanding of the role of the mechanistic target of rapamycin (mTOR) in cancer and aging. We also discuss the tumor immune surveillance system, and the need for a better understanding of its responses to mTOR inhibitors. We also address the issue of the misperception that rapamycin is a potent immunosuppressant. Finally, we review the current state of mTOR inhibitors in the cancer clinic. Because of the burgeoning elderly population most at risk for cancer, there is a great need for our eRapa findings to be a proof of concept for the development of new and more comprehensive approaches to cancer prevention that are safe and also mitigate other deleterious effects of aging.
authors.affiliation: Department of Molecular Medicine, Institute of Biotechnology, San Antonio, TX, USA.
authors.forename: Zelton Dave
authors.initials: ZD
authors.lastname: Sharp
authors.forename: Tyler Jay
authors.initials: TJ
authors.lastname: Curiel
authors.forename: Carolina Becker
authors.initials: CB
authors.lastname: Livi
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017173:Caenorhabditis elegans; D031204:Caloric Restriction; D004331:Drosophila melanogaster; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007165:Immunosuppression Therapy; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008017:Life Expectancy; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology*; D049490:Systems Biology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013995:Time
chemical_list: D000903:Antibiotics, Antineoplastic; D036341:Intercellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus