Anti-Cancer Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Michelle Prudhomme  
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France

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Targeting the Ubiquitin-Proteasome Pathway in Cancer Therapy

Author(s): Yuki Ishii, Samuel Waxman and Doris Germain

Affiliation: Mount Sinai School of Medicine,Department of Medicine, Division of Hematology/Oncology, One Gustave L. Levy Place, Box 1178, New York, NY 10029, USA.

Abstract:

The ubiquitin-proteasome pathway plays a central role in the degradation of proteins involved in several pathways including the cell cycle, cellular proliferation and apoptosis. Bortezomib is the first proteasome inhibitor to enter clinical use, and received approval by the Food and Drug Administration (FDA) for the treatment of patients with multiple myeloma, therefore validating inhibition of the proteasome as an anticancer target. The approval of Bortezomib was based on a large, international, multicenter phase III trial showing its efficacy and safety compared with conventional therapy. Preclinical data also demonstrates the synergistic effect of bortezomib with other chemotherapeutic agents and its ability to overcome drug resistance. Since then several other proteasome inhibitors have been developed. The anti-tumor activities of bortezomib have been attributed to its effect on pro-apoptotic pathways including the inhibition of NF-κB and induction of endoplasmic reticulum stress. However, the molecular mechanisms are not fully understood. In this review, we will summarize the molecular mechanism of apoptosis by bortezomib.

Keywords: dependent proteolysis, proteasome, bortezomib-induced apoptosis, cyclin D1

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Article Details

VOLUME: 7
ISSUE: 3
Page: [359 - 365]
Pages: 7
DOI: 10.2174/187152007780618180
Price: $58