pf-3758309 and Leukemia-Lymphoma--Adult-T-Cell

To evaluate therapeutic activity of PAK inhibition in ATLL and to characterize the role of PAK isoforms in cell proliferation, survival, and adhesion of ATLL cells in preclinical models.. Frequency and prognostic impact of. PAK1/2/4 are the three most abundantly expressed PAK family members in ATLL.. PAK2, a gene frequently amplified in ATLL, facilitates CADM1-mediated stromal interaction and promotes survival of ATLL cells. Taken together, PAK inhibition may hold significant promise as a targeted therapy for aggressive ATLLs.

Topics: Adult; Animals; Cell Adhesion; Cell Adhesion Molecule-1; Cell Line, Tumor; Cell Proliferation; Female; Gene Amplification; Humans; Leukemia-Lymphoma, Adult T-Cell; Mice; Mice, Inbred NOD; Mice, SCID; p21-Activated Kinases; Primary Cell Culture; Protein Kinase Inhibitors; Pyrazoles; Pyrroles; RNA, Small Interfering; Survival Rate; Xenograft Model Antitumor Assays