Proteosome Inhibitors Ps341 Bortezomib

Proteosomes are enzymes that mediate many critical cellular regulatory signals by degradation of the regulatory proteins or their inhibitors and, therefore, are potential therapeutic targets for cancer. Activity of several proteins shown to be overexpressed in MDS, such as nuclear factor kB (NF-kB), AP1, and E2F1, is partly dependent upon the 26S proteosome that can be selectively inhibited by bortezomib (formerly PS-341). This agent has been approved in 2003 for use in patients with relapsed multiple myeloma, and is currently being investigated in MDS trials.

Thirty-two patients with MDS were treated with bortezomib at Rush University Medical Center.28 All patients were treated at 1.5 mg/m2 once weekly for 4 weeks followed by a 2-week recovery. Twenty patients received at least two cycles; five patients (25%) had stable disease and seven (35%) showed a partial response. Further studies in MDS with bortezomib are awaited.

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