Targeted therapy in multiple myeloma.
BACKGROUND
Multiple myeloma (MM) is an incurable malignancy. Recent insights into its biology has allowed the use of novel therapies targeting not only the deregulated intracellular signaling in MM cells but also its interaction with the bone marrow microenvironment that confers drug resistance, growth, and survival advantage to the malignant cells.


METHODS
We review and summarize the recent advances in our knowledge of myeloma biology as well as the mechanism of action and clinical efficacy for novel therapeutic agents in clinical trials.


RESULTS
Several novel therapeutic agents are currently in clinical trials. Thalidomide is already established for both initial and salvage treatment. Bortezomib is being tested alone and in combination with conventional chemotherapy in various settings. Other agents are less effective in producing response but have been able to stabilize disease in patients with relapsed and/or refractory disease, such as arsenic trioxide, farnesyltransferase inhibitors, 2-methoxyestradiol, and vascular endothelial growth factor receptor inhibitors. Insights into drug resistance mechanism have also led to the development of novel agents that sensitize myeloma cells to chemotherapy (Bcl-2 antisense). Gene expression studies have in many instances identified pathways other than the intended target of the drug and have provided insights into the therapeutic mechanisms.


CONCLUSIONS
In the future, patients with MM will have more therapeutic options available than ever before. The challenge will be to identify patient subgroups that will benefit most from the different therapies and then determine how these biologically based therapies could be combined and incorporated into the overall management of patients.
Chng
Wee Joo
WJ
Department of Hematology-Oncology, National University Hospital, 119074 Singapore.
Lau
Lee Gong
LG
Yusof
Noorainun
N
Mow
Benjamin M F
BM
D000970:Antineoplastic Agents / Q000145:classification / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D002986:Clinical Trials as Topic; D016373:DNA, Antisense / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000639:trends*; D051231:Farnesyltranstransferase / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008148:Lovastatin / Q000627:therapeutic use; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000628:therapy; D010087:Oxides / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use; D013792:Thalidomide / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001152:Arsenicals; D001897:Boronic Acids; D016373:DNA, Antisense; D007166:Immunosuppressive Agents; D010087:Oxides; D011480:Protease Inhibitors; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D008148:Lovastatin; D051231:Farnesyltranstransferase; D000077237:Arsenic Trioxide