title: Combination of low doses of enzastaurin and lenalidomide has synergistic activity in B-non-Hodgkin lymphoma cell lines.
abstract: Less toxic and more active treatments are needed for indolent lymphomas as there is no curative treatment, and patients eventually die due to complications related to their disease. The purpose of the present study was to assess the antitumour activity of the combination of low doses of Enzastaurin and Lenalidomide (Revlimid) on B-lymphoma cell lines. The combination of Enzastaurin and Lenalidomide, at doses as low as 1 μM, showed strong synergism against indolent lymphomas by reducing cell growth, producing an increase in G0-G1 phase followed by significant decrease in S phase, increasing apoptosis, and inhibiting PI3K/AKT, PKC and MAPK/ERK pathways. These preclinical findings, together with promising results obtained with Lenalidomide for the treatment of non-Hodgkin lymphoma, suggest that further evaluation of the combination of Enzastaurin and Lenalidomide for the treatment of indolent lymphomas is warranted. These compounds, with a favourable toxicity profile, are not classic chemotherapeutic agents, causing severe side effects, and could be considered an example of a new innovative attempt of an anti-cancer 'soft treatment'.
authors.affiliation: Program of Innovative Therapies in Oncology and Haematology, Department of Oncology and Hematology, University of Modena and Reggio Emilia, Largo del Pozzo 71, 41124 Modena, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Cosenza
authors.forename: Monica
authors.initials: M
authors.lastname: Civallero
authors.forename: Giulia
authors.initials: G
authors.lastname: Grisendi
authors.forename: Luigi
authors.initials: L
authors.lastname: Marcheselli
authors.forename: Erika
authors.initials: E
authors.lastname: Roat
authors.forename: Alessia
authors.initials: A
authors.lastname: Bari
authors.forename: Stefano
authors.initials: S
authors.lastname: Sacchi
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D004357:Drug Synergism; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D000077269:Lenalidomide; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000473:pathology*; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D013792:Thalidomide; D000077269:Lenalidomide; C504878:enzastaurin