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The Proteasome as a Target for Cancer Treatment

Focus on Bortezomib

  • Review Article
  • Published:
American Journal of Cancer

Abstract

Targeted degradation of key regulatory proteins is an essential element of cell-cycle control. The proteasome plays a pivotal role in the degradation of such proteins and has, therefore, become an important therapeutic target for diseases involving cell proliferation, notably malignant diseases. Several studies have demonstrated that proteasome inhibition induces apoptosis and sensitizes cancer cells to traditional tumoricidal agents (chemotherapy or irradiation), both in vitroand in vivo, by having a significant impact on the turnover of certain key cell cycle regulatory elements (p53, p21, p27, Bax, etc.) as well as central transcription factors (nuclear factor [NF]-κB). Inhibition of the latter can result in reversal of chemoresistance.

Bortezomib, a potent and selective proteasome inhibitor, is particularly promising from a therapeutic perspective; it is the only such inhibitor that has progressed to clinical trials. Results from phase I/II studies indicate that the drug is well tolerated, and bortezomib has become an effective treatment for patients with hematologic malignancies (in particular multiple myeloma). This drug also seems to have significant activity in solid tumor malignancies. Phase I/II combination studies of bortezomib and other chemotherapeutics in hematologic and solid tumors are underway.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgments

Supported in part by CaPCURE and Millennium Pharmaceuticals, Inc. (clinical trial support).

The author has no conflicts of interest that are directly relevant to the content of this review.

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  1. The University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USA

    Christos N. Papandreou

  2. Department of Medical Oncology, School of Medicine, University of Thessaly, Larissa, 41110, Hellas, Greece

    Christos N. Papandreou

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Papandreou, C.N. The Proteasome as a Target for Cancer Treatment. Am J Cancer 4, 359–372 (2005). https://doi.org/10.2165/00024669-200504060-00003

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