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Cancer Chemotherapy and Pharmacology

Erschienen in:

14.02.2017 | Review Article

Asparaginase pharmacology: challenges still to be faced

verfasst von: Claudia Lanvers-Kaminsky

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 3/2017

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Abstract

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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Titel: Asparaginase pharmacology: challenges still to be faced
verfasst von: Claudia Lanvers-Kaminsky
Publikationsdatum: 14.02.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 3/2017
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-016-3236-y

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Efficacy and safety of neoadjuvant chemotherapy with oxaliplatin, 5-fluorouracil, and levofolinate for T3 or T4 stage II/III rectal cancer: the FACT trial

Evaluation of gefitinib efficacy according to body mass index, body surface area, and body weight in patients with EGFR-mutated advanced non-small cell lung cancer

Phase II study of bevacizumab and irinotecan as second-line therapy for patients with metastatic colorectal cancer previously treated with fluoropyrimidines, oxaliplatin, and bevacizumab

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Update Onkologie