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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Agammaglobulinaemia Tyrosine Kinase, Animals, Cell Line, Tumor, Class I Phosphatidylinositol 3-Kinases, Drug Synergism, Gene Expression Regulation, Neoplastic, Humans, Lymphoma, B-Cell, MAP Kinase Kinase Kinases, Mice, Molecular Targeted Therapy, Niacinamide, Protein-Tyrosine Kinases, Purines, Pyrazoles, Pyrimidines, Quinazolinones, Signal Transduction, Xenograft Model Antitumor Assays.
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Is combination of the MEK inhibitor pimasertib with BTK or PI3K-delta inhibitors active in preclinical models of aggressive lymphomas? Context: Lymphomas are among the most common human cancers and represent the cause of death for still too many patients. The B-cell receptor with its downstream signaling pathways represents an important therapeutic target for B-cell lymphomas. Here, we evaluated the activity of the MEK1/2 inhibitor pimasertib as single agent and in combination with other targeted drugs in lymphoma preclinical models. Cell lines derived mature B-cell lymphomas were exposed to increasing doses of pimasertib alone. Immunoblotting and gene expression profiling were performed. Combination of pimasertib with idelalisib or ibrutinib was assessed. Pimasertib as single agent exerted a dose-dependent antitumor activity across a panel of 23 lymphoma cell lines, although at concentrations higher than reported for solid tumors. Strong synergism was observed with pimasertib combined with the PI3K inhibitor idelalisib and the BTK inhibitor ibrutinib in cell lines derived from diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma. The data were confirmed in an in vivo experiment treating DLBCL xenografts with pimasertib and ibrutinib.
assistant
The data presented here provide the basis for further investigation of regimens including pimasertib in relapsed and refractory lymphomas. Final Decision: yes