Molecular mechanisms of effectiveness of novel therapies in multiple myeloma.
The prognosis of patients with multiple myeloma (MM) has radically changed over the past two decades mostly due to the introduction of novel pharmacologic treatments such as thalidomide, bortezomib and lenalidomide. These drugs were the first new anti-myeloma agents since the 1950s, and represented a landmark step in the race for the cure of MM and the paradigm of effectiveness of bench-to-bedside research. Compared to a median overall survival of 2-3 years in the mid-1950s, patients with MM have nowadays an expected median survival of 7-8 years. Novel agents have not only extended the life expectancy of patients with MM, but also shed light on the necessity of further understanding the biology of MM in order to design more effective, less toxic therapies. Basic research has provided a critical mass of information about the molecular and cellular biology of MM, particularly the pivotal pathogenetic role of the bone marrow niche. Several novel drugs, designed to specifically target MM in the context of its microenvironment, are currently in clinical trials and hold great promise for improving the MM treatment armamentarium and overcoming resistance. In this article we review the biological basis of effectiveness of anti-myeloma agents with an emphasis on experimental drugs.
Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
Giada
G
Bianchi
Irene M
IM
Ghobrial
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000187:drug effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects; D006801:Humans; D000860:Hypoxia; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D058990:Molecular Targeted Therapy; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D014176:Protein Biosynthesis / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D056811:Unfolded Protein Response / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007155:Immunologic Factors; D061988:Proteasome Inhibitors