title: Combinations of mTORC1 inhibitor RAD001 with gemcitabine and paclitaxel for treating non-Hodgkin lymphoma.
abstract: Single-agent mammalian target of rapamycin complex 1 (mTORC1) inhibitors have recently been reported as effective salvage treatment in non-Hodgkin lymphoma (NHL). The combined effect of mTORC1 inhibitor, RAD001, with chemotherapeutic agents used for relapsed or refractory NHL was examined. Synergistic interactions were observed for RAD001 plus gemcitabine or paclitaxel in six NHL cell lines; enhanced gemcitabine- and paclitaxel-induced caspase-dependent apoptosis associated with down-regulation of mTOR signaling was detected. Synergistic interactions were also observed with RAD001 plus gemcitabine and paclitaxel. In conclusion, synergistic cytotoxicity was observed with RAD001 plus gemcitabine and paclitaxel in NHL cells. Combination therapy with these three drugs should be examined in patients with refractory or relapsed NHL.
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chun-Te
authors.initials: CT
authors.lastname: Chiang
authors.forename: Pei-Yen
authors.initials: PY
authors.lastname: Yeh
authors.forename: Ming
authors.initials: M
authors.lastname: Gao
authors.forename: Chun-Wei
authors.initials: CW
authors.lastname: Chen
authors.forename: Ling-Chun
authors.initials: LC
authors.lastname: Yeh
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Feng
authors.forename: Sung-Hsin
authors.initials: SH
authors.lastname: Kuo
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Hsu
authors.forename: Yen-Shen
authors.initials: YS
authors.lastname: Lu
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D019169:Jurkat Cells; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000093542:Gemcitabine
chemical_list: D007166:Immunosuppressive Agents; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D003841:Deoxycytidine; D000068338:Everolimus; D058570:TOR Serine-Threonine Kinases; D020169:Caspases; D017239:Paclitaxel; D020123:Sirolimus; D000093542:Gemcitabine