The intrinsic pathway is initiated cell death is to mitochondria by a set of signals with the most important regulators in Bcl second The Bcl-2 antisense nucleotide was oblimersen evaluated in a Phase II trial in combination with rituximab in patients with relapsed B-cell NHL. An ORR of 42% was found and toxicity T is low grade and was reversible. ABT 263 is currently being evaluated in clinical trials for lymphomas as monotherapy and in combination with rituximab. The experimental inhibitor of Bcl 2, ABT 737 is in the pr Clinical development PHA-680632 for DLBCL and MCL. Other agents in the pr Clinical development obatoclax and YM155. 5.6. Kinase inhibitors. Aurora kinases A and B are oncogenic serine / threonine kinases that play an r Central role in the mitotic phase of the eukaryotic cell cycle. Overexpression of Aurora kinases w replace during the cell cycle, the control points Mitotic and the pin leads to aneuplo In many human cancers. Gene expression profiling in aggressive NHL of the B and T cells showed that Aurora kinases overexpressed to suggesting that they be genes of key components of the signing of proliferation.
MLN8237 is a selective inhibitor of AAK, the synergy with docetaxel showed in pr Clinical models of the MCL. In a Phase I trial in patients with advanced MP-470 malignant h Dermatological diseases, durable responses with neutropenia and thrombocytopenia were observed in the h Most frequent treatment-related adverse events. In a sp Later phase II study in patients with aggressive NHL is underway. The ABK selective inhibitor AZD1152 inhibits usen a variety of tumor xenografts in immunodeficient M And is currently in Phase I / II clinical development for DLBCL. Aurora kinases are in the pr Clinical development of new pan Aurora / JAK 2-kinase inhibitor AT9283. A series of cyclin-modulators are currently under development, including normal inhibitors of cyclin-dependent-Dependent kinase flavopiridol, which is in a phase I / II relapsed MCL / DLBCL and dinaciclib clinical reactions shown in a phase I heavily pretreated diffuse big cell lymphoma.
A Phase I dose escalation of cyclin D modulator ON 013,105 patients R / R’s lymphoma after. Shown promise in vitro and in vivo MCL Fostamatinib is a tyrosine kinase inhibitor spleen showed synergistic activity t with a number of agents in in vivo models DLBCL. In a recent Phase I / II in the NHL and CLL, the most important reactions have been observed in a number of tumor types. Common toxicity were diarrhea, fatigue, cytopenias and high blood pressure. The activation of protein kinase C and its overexpression was associated with a less favorable result of DLBCL. Enzastaurin is an inhibitor of PKC. In a Phase II study in R / R DLBCL freedom was ridiculed Ngerten progression-free with few grade 3 toxicity Observed t. Preferences INDICATIVE results of a subsequent Border study in aggressive NHL also show activity T alone. A Phase III study of enzastaurin t Possible to relapse in patients in remission after CHOP-R DLBCL prevent, is currently underway. Dasatinib is activity T as monotherapy in a Phase I / II R / R NHL shown. Pleural effusions and cytopenias were the main toxicity th Grade 3 or 4 A Phase II R / R DLBCL is currently recruiting. Bruton’s tyrosine kinase is a mediator of cell signaling and PCI B 32765 is a selective and irreversible inhibitor of Btk.