Novel treatment approaches for patients with multiple myeloma.
Treatment options for patients with multiple myeloma are a rapidly progressing area of clinical and scientific development. The discovery of key signaling pathways needed for myeloma cell growth and proliferation has resulted in a plethora of new and different treatment options. Chief among these new agents are the proteasome inhibitor bortezomib and the immunomodulatory agents thalidomide and lenalidomide. Efficacy for these agents has been extensively studied in the relapsed and refractory states, and more recently in induction therapy. Impressive responses have been observed in the induction and relapsed disease states, completely changing the disease treatment paradigms. Building on these successes and strong preclinical work, other signal transduction inhibitors are being tested in phase I and phase II clinical trials. These include agents that target histone acetylation, farnesylation, heat shock proteins, and direct AKT-targeting agents. Additionally, monoclonal antibody targets are being developed in an effort to target the tumor cells extracellularly. Clinical trial development based on preclinically designed rational combinations and targets have the potential to rapidly translate these findings into meaningful clinical responses.
Sinha
Rajni
R
Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA.
Kaufman
Jonathan L
JL
Lonial
Sagar
S
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D049109:Cell Proliferation / Q000187:drug effects; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D016503:Drug Delivery Systems; D015195:Drug Design; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D000077269:Lenalidomide; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D011480:Protease Inhibitors / Q000627:therapeutic use*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011719:Pyrazines / Q000627:therapeutic use*; D012008:Recurrence; D012074:Remission Induction; D015398:Signal Transduction; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use
D020533:Angiogenesis Inhibitors; D001897:Boronic Acids; D006360:Heat-Shock Proteins; D006657:Histones; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D051058:Oncogene Protein v-akt; D046988:Proteasome Endopeptidase Complex; D000077269:Lenalidomide