Novel Targets and Derived Small Molecule Inhibitors in Multiple Myeloma

Klaus      Podar

Abstract

Recent research advances have defined a key role of the bone marrow (BM) in multiple myeloma (MM) pathogenesis thereby leading to new treatment paradigms, which aim to target both the tumor cell as well as its BM microenvironment. The incorporation of thalidomide, bortezomib, and lenalidomide into conventional cytotoxic and transplantation regimens in relapsed and refractory, but also in newly diagnosed MM has changed treatment options during the last decade. However, MM remains still incurable. Ongoing translational research aims to identify additional therapeutic targets and to design derived agents, predominantly small molecule inhibitors, with higher potency and less toxicity to further improve MM patient outcome and to overcome drug resistance.

Keywords: Bone marrow microenvironment, bortezomib, carfilzomib, combination therapy, HDAC inhibitors, lenalidomide, multiple myeloma, pomalidomide, small molecule inhibitors, thalidomide, Array- comparative genomic hybridization, Extracellular signal related kinase, Farnesyltransferase inhibitors, Leukemia inhibitory factor, Microvessel density.