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Asparaginase pharmacology: Challenges still to be faced

Cancer Chemotherapy and Pharmacology, ISSN: 1432-0843, Vol: 79, Issue: 3, Page: 439-450
2017
  • 49
    Citations
  • 0
    Usage
  • 98
    Captures
  • 2
    Mentions
  • 33
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    49
  • Captures
    98
  • Mentions
    2
    • References
      2
      • Wikipedia
        2
  • Social Media
    33
    • Shares, Likes & Comments
      33
      • Facebook
        33

Review Description

Purpose The benefits of asparaginase (ASNASE) in the treatment of ALL and NHL are indisputable and new ASNASE preparations are under clinical development to overcome limitations of the actual ASNASE therapy, especially immunogenicity. Apart from ALL and NHL further indications of ASNASE are preclinically and clinically evaluated. Methods We reviewed ASNASE literature and especially focused on the mechanism of action, on biomarker, which determine ASNASE sensitivity and resistance, and on ASNASE pharmacodynamics in vivo. Results More than 40 years after the clinical introduction of ASNASE its mechanism of action is yet not fully understood. Studies on asparagine synthetase (ASNS) as biomarker for ASNASE resistance are contradictory and complicated by methodological obstacles. The role of glutamine hydrolysis for ASNASE efficacy is still debated, other mechanisms are possibly not yet identified. In addition, individual pharmacokinetic/-dynamic relationships cannot be properly addressed because of methodological limitations. Conclusion More sophisticated preclinical models and suitable methods for monitoring of ASNASE pharmacodynamics are urgently needed (1) to understand the mechanism of action, (2) to establish valid biomarkers for ASNASE sensitivity and resistance, (3) to evaluate the pharmacokinetics/-dynamics of ASNASEs in individual patients, and (4) to compare the bioequivalence of clinically established, as well as new ASNASE preparations.

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