Oncogenomics to Target Myeloma in the Bone Marrow Microenvironment

Multiple myeloma (MM) is an example of rapid bench-to-bedside translation in new drug development. Bortezomib and lenalidamide target the tumor cell in the bone marrow microenvironment to overcome drug resistance in laboratory and animal models; each is effective to treat relapsed and/or refractory, relapsed, and newly diagnosed MM, and both are now showing promise as maintenance therapy. Major ongoing translational research efforts include improved classification and personalized therapies; identification and validation of next-generation agents targeting the tumor cell in its microenvironment; novel immune therapies; rationally based combination therapies; and use of novel agents to delay or prevent development of active MM. This paradigm of targeting the tumor in its microenvironment has already extended median survival in MM from 3 to 7 to 8 years and has great potential to improve patient outcome in other hematologic malignancies and solid tumors as well. Clin Cancer Res; 17(6); 1225-33. (C)2011 AACR.