American Journal of Cancer

, Volume 3, Issue 5, pp 271–279 | Cite as

Proteasome inhibition

A novel approach to anticancer therapy
  • Paul G. Richardson
  • Teru Hideshima
  • Kenneth C. Anderson
Leading Article
  • 11 Downloads

Abstract

Proteasome inhibition is a new approach under investigation for cancer therapy. Protein degradation by the proteasome is a fundamental metabolic process. Inhibition of the proteasome has been shown to result in cell-cycle arrest and programmed cell death.

Bortezomib (Velcade®; formerly PS-341, Millennium Pharmaceuticals, Inc, Cambridge, Massachusetts) is the first proteasome inhibitor to enter clinical trials and is approved for the treatment of multiple myeloma in patients who have received at least two prior therapies and progressed on their last therapy. It is also being investigated for the treatment of a range of other cancers, both solid and hematologic. In preclinical studies, bortezomib causes apoptosis in cancer cells and seems to enhance the cytotoxicity of other conventional tumoricidal agents in human tumor cell lines, murine tumor models, and human xenograft models. In addition to targeting cancer cells directly, there is growing evidence that proteasome inhibition interferes with protective interactions between cancer cells and the bone marrow and may also act to prevent tumor-associated angiogenesis.

Preliminary data suggest that bortezomib inhibits proteasome activity in a dose-dependent and reversible manner, and has manageable toxicities. A phase II trial in relapsed and refractory multiple myeloma patients indicated that patients experienced substantial anticancer activity when treated with bortezomib monotherapy.

Notes

Acknowledgment

This review was supported by an unrestricted educational grant from Millennium Pharmaceuticals, Inc. Drs Richardson and Anderson have received honoraria for lectures and served on advisory boards for Millennium Pharmaceuticals Inc. Dr Hideshima has no conflicts of interest to declare.

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Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  • Paul G. Richardson
    • 1
  • Teru Hideshima
    • 1
  • Kenneth C. Anderson
    • 1
  1. 1.Jerome Lipper Multiple Myeloma Center, Division of Hematologic Oncology, Department of Adult OncologyDana-Farber Cancer Institute and Harvard Medical SchoolUSA

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