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.
The data presented here provide the basis for further investigation of regimens including pimasertib in relapsed and refractory lymphomas.
An abstract of a study by Tarantelli et al on the novel mTORC1/2 inhibitor PQR620 has in vitro and in vivo activity in lymphomas is presented. Proliferation and caspase 3/7 activation were assessed ...in 44 lymphoma cell lines treated with increasing doses of PQR620. Baseline gene expression profiling was obtained with the lllumina-HumanHT-12 Expression-BeadChips and analyzed with GSEA. Results indicated that PQR620 showed potent anti-proliferative activity in most of the cell lines tested. There was no association between sensitivity to PQR620 and TP53 inactivation. Apoptosis induction was seen more frequently with PQR620 than with the other 2 compounds: 6/44 cell lines for everolimus and 3/44 for AZD8055. The study concludes that PQR620 showed wide activity in lymphoma models as single agent and also in combination with venetoclax.
The main purpose of this book is to explore and understand the motivation behind major donations to higher education and what the role of religion is in these motivations. Features interviews with ...major donors.
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