title: Temsirolimus acts as additive with bendamustine in aggressive lymphoma.
abstract: The mammalian target of rapamycin (mTOR) is a protein kinase involved in the phosphatidylinositol 3-kinase (PI3K)/AKT signalling pathway. It plays a pivotal role in the control of cell proliferation, survival, and angiogenesis with multiple and frequent dysregulations of this pathway in human tumors. Temsirolimus is an intravenous drug, specifically inhibiting the mTOR pathway. Bendamustine is well known for its clinical activity in indolent non-Hodgkin-lymphoma (NHL) and has lately shown clinical activity in mantle cell lymphoma (MCL). Here, we present a case report of temsirolimus in combination with bendamustine and rituximab leading to a CR in a pretreated male. In addition, our in vitro data underlines the additive and synergistic efficacy in cell growth reduction of temsirolimus combined with bendamustine in MCL cell lines and in DLBCL cell lines. Furthermore, as an underlying mechanism of this additive, effects on cell cycle inhibition and apoptosis induction could be identified.
authors.affiliation: Department of Internal Medicine III, University Hospital Munich-Großhadern, Marchioninistr. 15, 81377, Munich, Germany. anna.zoellner@med.lmu.de.|Clinical Cooperative Group Leukemia, Helmholtz Zentrum Munich, Munich, Germany. anna.zoellner@med.lmu.de.
authors.forename: Anna-Katharina
authors.initials: AK
authors.lastname: Zoellner
authors.affiliation: Department of Internal Medicine III, University Hospital Munich-Großhadern, Marchioninistr. 15, 81377, Munich, Germany.|Clinical Cooperative Group Leukemia, Helmholtz Zentrum Munich, Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Weiglein
authors.affiliation: Clinical Cooperative Group Leukemia, Helmholtz Zentrum Munich, Munich, Germany.
authors.forename: Grit
authors.initials: G
authors.lastname: Hutter
authors.affiliation: Clinical Cooperative Group Leukemia, Helmholtz Zentrum Munich, Munich, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Zimmermann
authors.affiliation: Clinical Cooperative Group Leukemia, Helmholtz Zentrum Munich, Munich, Germany.
authors.forename: Hans Christian
authors.initials: HC
authors.lastname: Cieplik
authors.affiliation: Department of Internal Medicine III (Hematology, Oncology, and Pneumology), University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Hess
authors.affiliation: Department of Internal Medicine III, University Hospital Munich-Großhadern, Marchioninistr. 15, 81377, Munich, Germany.|Clinical Cooperative Group Leukemia, Helmholtz Zentrum Munich, Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Dreyling
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000069461:Bendamustine Hydrochloride / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D004357:Drug Synergism; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000175:diagnosis* / Q000188:drug therapy*; D008297:Male; D000069283:Rituximab / Q000008:administration & dosage; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000970:Antineoplastic Agents; D000069283:Rituximab; C401859:temsirolimus; D000069461:Bendamustine Hydrochloride; D020123:Sirolimus
keywords: Bendamustine; DLBCL; MCL; Temsirolimus