title: Asparaginase pharmacology: challenges still to be faced.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital of Muenster, Albert-Schweitzer-Campus 1, A1, 48149, Muenster, Germany. lanvers@uni-muenster.de.
authors.forename: Claudia
authors.identifier: 0000-0002-9764-8035
authors.initials: C
authors.lastname: Lanvers-Kaminsky
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001215:Asparaginase / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D001215:Asparaginase
keywords: Asparaginase; Asparagine synthetase; Drug resistance; Glutaminase; Pharmacodynamics