Estrogenic or antiestrogenic therapies for multiple myeloma?
Multiple myeloma (MM) is a common hematological malignancy which remains incurable due to both intrinsic and acquired resistance to conventional or more novel drugs. Estrogenic and antiestrogenic compounds are very promising drugs for the treatment of MM. Indeed, they inhibit cell proliferation in vitro. They block cell cycle and/or induce apoptosis even in drug-resistant MM cells but not normal B cells. They interfere with survival pathways often deregulated in myelomas. They co-operate with conventional drugs to enhance apoptosis or to overcome resistance. In vivo, they act also on tumoral angiogenesis in xenograft models. As a whole, they possess all the criteria which render them attractive for a new therapeutic strategy. Importantly, they are well-tolerated at the doses tested in vitro or in vivo, encouraging the rapid onset of critical trials.
Sola
Brigitte
B
Biologie moléculaire et cellulaire de la signalisation, IFR 146, Université de Caen, Caen, France. brigitte.sola@unicaen.fr
Renoir
Jack-Michel
JM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism; D004965:Estrogen Antagonists / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010954:Plasmacytoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011960:Receptors, Estrogen / Q000819:agonists / Q000187:drug effects* / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D015398:Signal Transduction
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D004958:Estradiol; D020169:Caspases