Aminopeptidases in Cancer, Biology and Prospects for Pharmacological Intervention

Sarah A. Holstein, Caroline A. Heckman, Faith E. Davies, Gareth J. Morgan, Stefan Svensson Gelius, Fredrik Lehmann

Research output: Contribution to journalReview articlepeer-review

6 Scopus citations

Abstract

Aminopeptidases, which catalyze the cleavage of amino acids from the amino terminus of proteins, are widely distributed in the natural world and play a crucial role in cellular processes and functions, including metabolism, signaling, angiogenesis, and immunology. They are also involved in the homeostasis of amino acids and proteins that are required for cellular proliferation. Tumor cells are highly dependent on the exogenous supply of amino acids for their survival, and overexpression of aminopeptidase facilitates rapid tumor cell proliferation. In addition, clinical studies have demonstrated that patients with cancers with high aminopeptidase expression often have poorer outcomes. Emerging evidence supports the rationale of inhibiting aminopeptidase activity as a targeted approach for novel treatment options, as limiting the availability of amino acids can be selectively lethal to tumor cells. While there are agents that directly target aminopeptidases that demonstrate potential as cancer therapies, such as bestatin and tosedostat, more selective and more targeted therapeutic approaches are needed. This article specifically looks at the biological role of aminopeptidases in both normal and cancer processes, and their potential as a biological target for future therapeutic strategies. When examining previous publications, most do not cover aminopeptidases and their role in cancer processes. Aminopeptidases play a vital role in cell processes and functions; however, their overexpression may lead to a rapid proliferation of tumor cells. Emerging evidence supports the rationale of leveraging aminopeptidase activity as a targeted approach for new oncological treatments. This article specifically looks at the biological role of aminopeptidases in both normal and cancer processes, and their potential as a biological target for future therapeutic strategies.

Original languageEnglish (US)
Pages (from-to)25-46
Number of pages22
JournalCurrent Cancer Drug Targets
Volume23
Issue number1
DOIs
StatePublished - Jan 2023

Keywords

  • Cancer
  • amino acids
  • angiogenesis
  • metabolism
  • peptidase
  • peptidase inhibitor
  • peptide drug conjugates
  • unfolded protein response

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Drug Discovery
  • Cancer Research

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