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Arginine deprivation as a targeted therapy for cancer

L Feun1, M You, C J Wu

  • 1Hematology/Oncology, University of Miami School of Medicine, 1201 N.W. 16th Street, Miami, FL. 33136, USA. lfeun@med.miami.edu

Current Pharmaceutical Design
|May 14, 2008
PubMed

Insights

Arginine deprivation using ADI-PEG20 targets cancers lacking argininosuccinate synthetase (ASS). This novel cancer therapy demonstrated antitumor activity in clinical trials for melanoma and hepatocellular carcinoma.

Area of Science:

  • Biochemistry
  • Oncology
  • Enzymology

Background:

  • Certain cancers exhibit auxotrophy for specific amino acids, making amino acid deprivation a potential therapeutic strategy.
  • Arginine deprivation is a novel approach targeting tumors with low or absent argininosuccinate synthetase (ASS) expression.
  • ASS is crucial for arginine synthesis; its absence in tumors like melanoma and hepatocellular carcinoma creates a vulnerability.

Purpose of the Study:

  • To review the laboratory and clinical experience with arginine deiminase pegylated-20 (ADI-PEG20) as an antineoplastic agent.
  • To discuss the potential of ADI-PEG20 in treating cancers auxotrophic for arginine.
  • To explore future directions for ADI-PEG20 utilization in cancer therapy.

Main Methods:

  • Utilizing arginine deiminase (ADI), a microbial enzyme, to degrade arginine and induce deprivation.
  • Formulating a pegylated version, ADI-PEG20, for enhanced stability and efficacy.
  • Conducting in vitro and in vivo studies, including Phase I and II clinical trials.

Main Results:

  • ADI-PEG20 demonstrated in vitro and in vivo activity against melanoma and hepatocellular carcinoma.
  • ADI-PEG20 was shown to induce apoptosis in melanoma cell lines.
  • Clinical trials showed demonstrated antitumor activity of ADI-PEG20 in patients with melanoma and hepatocellular carcinoma.

Conclusions:

  • Arginine deprivation via ADI-PEG20 is a promising therapeutic strategy for ASS-deficient tumors.
  • ADI-PEG20 exhibits significant antitumor activity in preclinical and clinical settings.
  • Further research and clinical trials are warranted to optimize the use of ADI-PEG20 in cancer treatment.

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