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Drug Discov Today. 2003 Apr 1;8(7):307-15.

Potential for proteasome inhibition in the treatment of cancer.

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Millennium Pharmaceuticals, 35 Landsdowne Street, Cambridge, MA 02139, USA.


Proteasome inhibition is a new approach to treating cancer. Proteasome inhibitors specifically induce apoptosis in cancer cells, but most proteasome inhibitors are not suitable for clinical development. Peptide boronates overcome the shortcomings of earlier generation proteasome inhibitors, and bortezomib (VELCADE; formerly PS-341) is the first peptide boronate to enter clinical trials. Preclinical studies of bortezomib have demonstrated antitumor activity in a variety of tumor types. Phase I trials provided evidence of manageable toxicities and support a twice-weekly dosing regimen now being examined in a Phase III study.

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