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<p>Abstract</p> <p>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 <it>in vitro</it>. 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. <it>In vivo</it>, 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 <it>in vitro </it>or <it>in vivo</it>, encouraging the rapid onset of critical trials.</p>