The ubiquitin-proteasome system as a molecular target in solid tumors: An update on bortezomib

A. Milano, F. Perri, Francesco Caponigro

Research output: Contribution to journalArticlepeer-review

Abstract

The ubiquitin-proteasome system has become a promising molecular target in cancer therapy due to its critical role in cellular protein degradation, interaction with cell cycle and apoptosis regulation, and unique mechanism of action. Bortezomib (PS-341) is a potent and specific reversible proteasome inhibitor, which has shown strong in vitro antitumor activity as single agent and in combination with other cytotoxic drugs in a broad spectrum of hematological and solid malignancies. In preclinical studies, bortezomib induced apoptosis of malignant cells through the inhibition of NF-κB and stabilization of pro-apoptotic proteins. Bortezomib also promotes chemo- and radiosensitization of malignant cells in vitro and inhibits tumor growth in murine xenograft models. The proteasome has been established as a relevant target in hematologic malignancies and bortezomib has been approved for the treatment of multiple myeloma. This review summarizes recent data from clinical trials in solid tumors.

Original languageEnglish
Pages (from-to)171-178
Number of pages8
JournalOncoTargets and Therapy
Volume2
Publication statusPublished - 2009

Keywords

  • Bortezomib
  • Clinical studies
  • NF-κB
  • Proteasome
  • Solid tumors

ASJC Scopus subject areas

  • Oncology
  • Pharmacology (medical)

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