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Aminopeptidases in Cancer, Biology and Prospects for Pharmacological Intervention

Holstein, Sarah A. (author)
Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE USA.
Heckman, Caroline A. (author)
Univ Helsinki, Inst Mol Med Finland, Helsinki Inst Life Sci, iCAN Digital Precis Canc Med Flagship, Helsinki, Finland.
Davies, Faith E. (author)
NYU Langone Hlth, Perlmutter Canc Ctr, New York, NY USA.
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Morgan, Gareth J. (author)
NYU Langone Hlth, Perlmutter Canc Ctr, New York, NY USA.
Svensson Gelius, Stefan (author)
Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
Lehmann, Fredrik (author)
Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE USA Univ Helsinki, Inst Mol Med Finland, Helsinki Inst Life Sci, iCAN Digital Precis Canc Med Flagship, Helsinki, Finland. (creator_code:org_t)
Bentham Science Publishers, 2023
2023
English.
In: Current Cancer Drug Targets. - : Bentham Science Publishers. - 1568-0096 .- 1873-5576. ; 23:1, s. 25-46
  • Research review (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Keyword

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

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