byl719 and Lymphoma--Mantle-Cell

Acquired resistance to cancer drugs is common, also for modern targeted drugs like the Bruton tyrosine kinase (BTK) inhibitor ibrutinib, a new drug approved for the treatment of the highly aggressive and relapsing mantle cell lymphoma (MCL). The tumor microenvironment often impacts negatively on drug response. Here, we demonstrate that stromal cells protect MCL cells from ibrutinib-induced apoptosis and support MCL cell regrowth after drug removal by impairing ibrutinib-mediated downregulation of PI3K/AKT signaling. Importantly, the stromal cell-mediated ibrutinib resistance was overcome

Topics: Adenine; Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Line; Cell Line, Tumor; Class I Phosphatidylinositol 3-Kinases; Drug Resistance, Neoplasm; Humans; Interleukin Receptor Common gamma Subunit; Lymphoma, Mantle-Cell; Mice, Inbred NOD; Mice, Knockout; Mice, SCID; Piperidines; Pyrazoles; Pyrimidines; Stromal Cells; Thiazoles; Tumor Burden; Xenograft Model Antitumor Assays