title: Rapamycin and mTORC1 inhibition in the mouse: skin cancer prevention.
abstract: Therapeutic and preventive effects of rapamycin include reduced risk of nonmelanoma skin cancer (NMSC). In this issue of the journal (beginning on page 1011), Checkley and colleagues report that rapamycin inhibits mTOR complex 1 in murine epidermis, thereby inhibiting tumor promotion mediated by tetradecanoyl phorbol-13 acetate in association with a strong anti-inflammatory effect. Rapamycin is an immunosuppressive drug for preventing graft rejection in organ transplant recipients and reduces the risk of NMSC and Kaposi's sarcoma in this population, albeit by mechanisms distinct from immunosuppression. Important future directions include identifying molecular predictors of rapamycin/rapalog sensitivity or resistance (potentially, for example, PI3K pathway alterations and KRAS mutations) and combined non-rapalog, mTOR-targeting approaches, all of which should increase efficacy and minimize toxicity.
authors: Department of Dermatology, Skin Diseases Research Center and UAB Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors: Mohammad
authors: M
authors: Athar
authors: Levy
authors: L
authors: Kopelovich
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002273:Carcinogens / Q000633:toxicity*; D006801:Humans; D010212:Papilloma / Q000517:prevention & control*; D012878:Skin Neoplasms / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
chemical_list: D000903:Antibiotics, Antineoplastic; D016588:Anticarcinogenic Agents; D002273:Carcinogens; D013755:Tetradecanoylphorbol Acetate