New drugs in multiple myeloma: mechanisms of action and phase I/II clinical findings.
The outcome of multiple myeloma has substantially improved over the past decade, mainly due to recently approved drugs, such as thalidomide, lenalidomide, and bortezomib. Nevertheless, most patients still relapse and, therefore, drugs with new mechanisms of action are urgently needed to overcome this resistance. In this Review, we discuss some of the new targeted therapeutic strategies under assessment in preclinical and clinical studies in multiple myeloma. Unfortunately, the single-agent clinical activity of most of these new drugs has been limited; nevertheless, their effectiveness might be enhanced by their rational combination with each other or with conventional agents.
Ocio
Enrique M
EM
Servicio de Hematología, Hospital Universitario de Salamanca, Salamanca, Spain.
Mateos
María-Victoria
MV
Maiso
Patricia
P
Pandiella
Atanasio
A
San-Miguel
Jesús F
JF
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000954:Antigens, Surface / Q000187:drug effects; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D019175:DNA Methylation / Q000187:drug effects; D047630:Depsipeptides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044127:Epigenesis, Genetic / Q000187:drug effects; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000503:physiopathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009842:Oligopeptides / Q000494:pharmacology; D010087:Oxides / Q000494:pharmacology; D010456:Peptides, Cyclic; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011494:Protein Kinases / Q000187:drug effects; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000970:Antineoplastic Agents; D001152:Arsenicals; D015853:Cysteine Proteinase Inhibitors; D047630:Depsipeptides; D004791:Enzyme Inhibitors; D006360:Heat-Shock Proteins; D056572:Histone Deacetylase Inhibitors; D016328:NF-kappa B; D009842:Oligopeptides; D010087:Oxides; D010456:Peptides, Cyclic; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011956:Receptors, Cell Surface; C090535:benzyloxycarbonyl-isoleucyl-glutamyl(O-tert-butyl)-alanyl-leucinal; D013186:Farnesyl-Diphosphate Farnesyltransferase; D011494:Protein Kinases; C546842:MTOR protein, human; D020794:Receptor Protein-Tyrosine Kinases; D058570:TOR Serine-Threonine Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D000077237:Arsenic Trioxide; C098980:plitidepsin