Over-expression of Aurora kinases throughout the cell cycle can over-ride mitotic and spindle checkpoints resulting in aneuploidy in many human cancers. Gene expression profiling in aggressive B and T cell NHL has shown the Aurora kinases to be overexpressed indicating that they may be crucial element genes of the proliferative signature. MLN8237 is just a particular FK866 clinical trial AAK inhibitor, which confirmed synergy with docetaxel in pre-clinical models of MCL. In a phase I study in patients with advanced level hematologic malignancies, durable reactions were observed, with neutropenia and thrombocytopenia being the most typical treatment-related adverse events. A subsequent phase II study in patients with aggressive NHL is continuing. The selective ABK chemical, AZD1152, potently inhibited a selection of cyst xenografts in immunodeficient mice and is currently in phase I/II development for DLBCL. Aurora kinases in preclinical development include the novel pot Mitochondrion Aurora/JAK 2 kinase inhibitor AT9283. Numerous cyclin modulators are currently in development, like the cyclin conditional kinase inhibitors flavopiridol, which is in a phase I/II study in relapsed MCL/DLBCL, and dinaciclib, which indicates clinical responses in a phase I study in heavily pre-treated diffuse large-cell lymphoma. A phase I dose escalation study of the cyclin D modulator ON 013105 in patients with R/R lymphoma is continuing after showing promising in vitro and in vivo data in MCL. Fostamatinib can be a spleen tyrosine kinase inhibitor which has shown synergistic action using a variety of agents in in vivo models of DLBCL. In a current stage I/II study in CLL and NHL, large responses were noticed in several tumor types. Popular toxicities involved exhaustion, diarrhea, cytopenias, and hypertension. Activation of protein kinase C and its overexpression have ALK inhibitor been associated with a less favorable result in DLBCL. Enzastaurin can be an inhibitor of PKC T. In a phase II study in R/R DLBCL, extended freedom from progression was observed with little grade 3 toxicity. Preliminary results from the subsequent review in aggressive NHL also reveal single agent activity. A phase III study with daily enzastaurin to prevent relapse in people in remission after Dhge CHOP therapy is ongoing. Dasatinib shows single agent activity in a stage I/II study in R/R NHL. Cytopenias and pleural effusions were the principle grade a few toxicities. A phase II study in R/R DLBCL is currently recruiting. Brutons tyrosine kinase is a mediator of T cell signaling, and PCI 32765 is really a selective, irreversible inhibitor of Btk. In a phase I study in patients with R/R B cell malignancies, PCI 32765 caused sturdy reactions with little toxicity. Encouraging preliminary clinical results with the anaplastic lymphoma kinase chemical crizotinib in sophisticated chemoresistant ALK lymphoma patients have also been observed. The benzimidazole AZD6244 is a novel, 2nd era mitogen-activated protein kinase inhibitor.