title: Activity of BKM120 and BEZ235 against Lymphoma Cells.
abstract: Non-Hodgkin lymphomas encompass a heterogeneous group of cancers, with 85-90% arising from B lymphocytes and the remainder deriving from T lymphocytes or NK lymphocytes. These tumors are molecularly and clinically heterogeneous, showing dramatically different responses and outcomes with standard therapies. Deregulated PI3K signaling is linked to oncogenesis and disease progression in hematologic malignancies and in a variety of solid tumors and apparently enhances resistance to antineoplastic therapy, resulting in a poor prognosis. Here, we have evaluated and compared the effects of the pan-PI3K inhibitor BKM120 and the dual PI3K/mTOR inhibitor BEZ235 on mantle, follicular, and T-cell lymphomas. Our results suggest that BKM120 and BEZ235 can effectively inhibit lymphoma cell proliferation by causing cell cycle arrest and can lead to cell death by inducing apoptosis and autophagy mediated by ROS accumulation. Despite great advances in lymphoma therapy after the introduction of monoclonal antibodies, many patients still die from disease progression. Therefore, novel treatment approaches are needed. BKM120 and BEZ235 alone and in combination are very effective against lymphoma cells in vitro. If further studies confirm their effectiveness in animal models, they may be promising candidates for development as new drugs.
authors.affiliation: Program of Innovative Therapies in Oncology and Haematology, Department of Diagnostic and Clinical Medicine and Public Health, University of Modena and Reggio Emilia, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Civallero
authors.affiliation: Program of Innovative Therapies in Oncology and Haematology, Department of Diagnostic and Clinical Medicine and Public Health, University of Modena and Reggio Emilia, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Cosenza
authors.affiliation: Program of Innovative Therapies in Oncology and Haematology, Department of Diagnostic and Clinical Medicine and Public Health, University of Modena and Reggio Emilia, Italy.
authors.forename: Samantha
authors.initials: S
authors.lastname: Pozzi
authors.affiliation: Program of Innovative Therapies in Oncology and Haematology, Department of Diagnostic and Clinical Medicine and Public Health, University of Modena and Reggio Emilia, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Bari
authors.affiliation: Department of Diagnostic, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Ferri
authors.affiliation: Program of Innovative Therapies in Oncology and Haematology, Department of Diagnostic and Clinical Medicine and Public Health, University of Modena and Reggio Emilia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Sacchi
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008228:Lymphoma, Non-Hodgkin; D009025:Morpholines / Q000494:pharmacology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011379:Prognosis; D011804:Quinolines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000631:Aminopyridines; D000970:Antineoplastic Agents; D007093:Imidazoles; D009025:Morpholines; C571178:NVP-BKM120; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011804:Quinolines; D017382:Reactive Oxygen Species; C531198:dactolisib