Therapeutic Utility of Proteasome Inhibitors for Acute Leukemia

摘要: The proteasome inhibitors have emerged as a new and promising class of cancer therapeutics for hematological malignanices. In multiple myeloma mantle cell lymphoma, bortezomib is the first-in-class inhibitor to be approved by US Food Drug Administration treatment these malignancies. vitro in vivo data are suggestive utility acute leukemias importantly, Phase-I clinical trial adult leukemia patients demonstrated biological activity (Cortes et al., Clin Cancer Res. 10:3371-3376, 2004). Here, we describe rationale targeting proteasome, molecular pharmacology summarize results from trials using single agents component multidrug combination therapies. lymphoblastic (ALL) with refractory disease poor outcomes, represent an untapped therapeutic resource. Since low doses display striking synergy other such epigenetically targeted drugs (Miller al. (Blood. 110:267-277, 2007) 113(18):4289-4299, 2009)), investigations hold promise pediatric young patients, where long-term toxicities late effects could minimized optimizing use this drugs.