title: Sirolimus plus gemcitabine: a new therapeutic combination for resistant sarcomas?
abstract: Sarcomas are a rare family of heterogeneous tumors of mesenchymal origin characterized by their bad prognosis. In addition, limited active therapeutic options are available. The cytotoxic drug gemcitabine and the inhibition of the mTOR pathway have demonstrated modest activity in sarcomas as monotherapy. However, preclinical data suggest that the combination of both treatments results in enhanced antitumor activity. In vitro and in vivo experiments with the mTOR inhibitor sirolimus plus gemcitabine showed dramatic results in preclinical models of sarcoma. Moreover, a Phase I study demonstrated the favorable toxicity profile of the combination in patients with advanced solid tumors. Therefore, treatment with sirolimus plus gemcitabine deserves further investigation in sarcomas.
authors.affiliation: The Royal Marsden Hospital, Fulham Road, SW3 6JJ, London, UK.
authors.forename: Juan
authors.initials: J
authors.lastname: Martin-Liberal
authors.forename: Oscar M
authors.initials: OM
authors.lastname: Tirado
authors.forename: Xavier
authors.initials: X
authors.lastname: García del Muro
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D019008:Drug Resistance, Neoplasm; D006801:Humans; D011379:Prognosis; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D020123:Sirolimus / Q000008:administration & dosage; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus; D000093542:Gemcitabine
keywords: gemcitabine; rapamycin; sirolimus; soft tissue sarcoma