Mechanisms of drug resistance and sensitivity concerning novel agents for multiple myeloma.
Multiple myeloma (MM) is a neoplastic plasma-cell disorder characterized by clonal proliferation of malignant plasma cells in the bone marrow microenvironment. Novel treatments such as proteasome inhibitors and immunomodulatory agents significantly prolong both progression free survival and overall survival (OS) in patients with MM. However, recent clinical data have indicated that it is difficult to eradicate all MM clones even with the administration of such novel agents. To overcome drug resistance (DR), further investigation of the mechanism underlying DR is required, and strategies to up-regulate, maintain, and restore drug sensitivity will become increasingly important in the clinical setting. The findings from basic research focusing on the microenvironment, genetic abnormalities, and signal transduction disturbances related to MM pathogenesis are excellent strategies for developing new agents. In addition, based on the improved OS over 10 years and the low continuation rate of standard therapy in frail patients, a stratified strategy has the potential to provide total therapy.
Saitama Medical Center, Saitama Medical University, Department of Hematology.
Michihide
M
Tokuhira
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002448:Cell Adhesion / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents