Targeting of NF-kappaB signaling pathway, other signaling pathways and epigenetics in therapy of multiple myeloma.

Targeting of NF-kappaB signaling pathway, other signaling pathways and epigenetics in therapy of multiple myeloma. Cardiovasc Hematol Disord Drug Targets. 2013 Mar 1;13(1):16-34 Authors: Fuchs O Abstract Multiple myeloma (MM) remains an incurable disease, at least for the big majority of patients, in spite of the great progress with new drugs in the last years. New treatment strategies are needed to improve the outcome of patients. NF-κB activation in MM is caused by mutations in the factors involved in the NF-κB pathways contributing to their dysregulation and by signals from the bone marrow microenvironment. Agents with NF-κB inhibitory activity enhance the anti-MM effects of conventional chemotherapeutic agents. Bortezomib was the first approved member of a new class of anti-MM agents, the proteasome inhibitors. At least, five proteasome inhibitors of the next generation with greater efficacy (carfilzomib, marizomib (salinosporamide A, NPI-0052), threonine boronic acid-derived proteasome inhibitor CEP-18770, the peptide-semicarbazone S-2209, the tripeptide mimetic BSc2118, and MLN9708/2238) have been recently tested in preclinical models of MM. Carfilzomib has been recently approved for the treatment of patients with MM who have received at least two prior therapies, including bortezomib and immunomodulatory derivatives (IMiDs, thalidomide, lenalidomide or pomalidomide). More specific IκB kinase inhibitors were also used in pr...
Source: Cardiovascular and Hematological Disorders Drug Targets - Category: Drugs & Pharmacology Tags: Cardiovasc Hematol Disord Drug Targets Source Type: research