Nitroimidazo oxazines were found to be more advanced than the CGI 17341 substances due

This differential regulation of cytokine activity, and specially IL 6 activity, supplies the basis for lenalidomide altering the bone marrow micro-environment when the expression of proinflammatory cytokines is very important for the development and survival of MM cells. Furthermore, inhibition enzalutamide of VEGF by lenalidomide might alter the bone-marrow microvasculature, thus making the cyst microenvironment less favorable for MM cell development, migration, and survival. VEGF inhibition probably occurs via the PI3K/Akt signaling pathway, which normally becomes phosphorylated in reaction to VEGF stimulation. Lenalidomide is up to 2000 times more potent than thalidomide in stimulating the expansion of T cells and up to times more potent at raising the release of IL 2 and interferon. This T cell costimulatory activity Organism shows that lenalidomide is able to act as an adjuvant to promote type 1 cell mediated anti-tumor immune responses involving equally CD4 T helper cells and CD8 cytotoxic T cells. The capability of lenalidomide to boost activator protein 1 and NF B action in antigen primed T cells has been proposed as a T cell costimulatory system, which may not simply defeat T cell anergy, but in addition potentiates any non T cell receptor mediated signaling. Along with improving the adaptive immune response, there is also evidence that lenalidomide could enhance innate immunity and natural killer cell mediated lysis of MM cells particularly via its consequences on IL 2 production by T cells. Lenalidomide continues to be proven to directly potentiate apoptosis of MM cells via several pathways. These generally include inhibition of expression of the cellular inhibitor of apoptosis protein 2, potentiation of the actions of other apoptosis inducers such as TNF related apoptosisinducing ligand, increased sensitivity to Fas induction, and improved caspase 8 activation. Caspase 8, a built-in component of Fas mediated apoptosis, is sharply upregulated by BMN 673 lenalidomide. 63 In addition, dexamethasone activates caspase 9 indicating that the two drugs in combination create double signs with the capacity of increased cell death. Lenalidomide is related to direct anti-proliferative action against MM cells in the lack of immune cells or proapoptotic components by causing G1 growth arrest. Essentially, lenalidomide inhibits the proliferation of malignant T cells while protecting normal CD34 progenitor cells. The different mechanisms of action of lenalidomide are summarized in Figure 4. Scientific evidence for lenalidomide in MM Newly identified disease Lenalidomide isn't yet accepted for use in patients with previously untreated disease. Nevertheless, many clinical studies have reported promising response and survival outcomes in this group of patients.