HtrA serine proteases as potential therapeutic targets in cancer

Jeremy Chien, Mara Campioni, Viji Shridhar, Alfonso Baldi

Research output: Contribution to journalReview article

93 Scopus citations

Abstract

The human HtrA family of serine proteases consists of four members: HtrA1, HtrA2, HtrA3 and HtrA4. Although prokaryotic HtrA proteins are well characterized in their dual roles as chaperones and proteases that degrade misfolded proteins in the periplasm, some members of mammalian HtrA proteins are described as potential modulators of programmed cell death and chemotherapy-induced cytotoxicity. Goal of this review article is to describe the molecular alterations associated with these HtrA serine proteases and how these alterations may be associated with tumor behavior and response to chemotherapy. We will also discuss evidence that chemotherapeutic drugs regulate the expression and activation of HtrA serine proteases and that these proteases contributes to programmed cell death. Finally, we will discuss the potential role of epigenetic therapy in targeting the expression and activation of HtrA serine proteases and the mechanisms by which these proteases enhance cytotoxic effect of conventional chemotherapy.

Original languageEnglish (US)
Pages (from-to)451-468
Number of pages18
JournalCurrent Cancer Drug Targets
Volume9
Issue number4
DOIs
StatePublished - Jun 2009

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Drug Discovery
  • Cancer Research

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