Expanding Targets for a Metabolic Therapy of Cancer: LAsparaginase
Pp. 418-445 (28)
Daniele Covini, Maristella Maggi, Saverio Tardito, Ovidio Bussolati, Laurent R. Chiarelli, Maria V. Pasquetto, Luca Vecchia, Giovanna Valentini and Claudia Scotti
The antitumour enzyme L-asparaginase (L-Asparagine amidohydrolase, EC
220.127.116.11, ASNase) catalyzes the deamination of L-asparagine to L-Asp and ammonia and
has been used for many years in the treatment of acute lymphoblastic leukaemia,
Natural Killer cells tumors, subtypes of myeloid leukaemias and T-cell lymphomas.
Recently, ovarian carcinomas and other solid tumours have been proposed as additional
targets for ASNase, due to its potential role for its glutaminase activity. The increasing
attention devoted to the antitumor activity of ASNase prompted us to analyze recent
patents specifically concerning this enzyme. An overview of metabolic pathways
affected by Asn and Gln depletion along with potential targets of ASNase is discussed.
In particular, attention has been paid to novel ASNases, especially the Helicobacter
pylori one, and those with amino acid substitutions aimed at improving enzymatic
activity of the classical Escherichia coli enzyme. An effort has also been made to
include modifications, such as natural glycosylation or synthetic conjugation with other
molecules, introduced for therapeutic purposes. Finally, available patent information on
biotechnological protocols and strategies applied to production of ASNase as well as to
its administration and delivery in organisms has been analyzed.
Acute lymphoblastic leukaemia, ALL, amino acid metabolism, amino acid transporters, ASNase, asparagine, asparagine synthetase, cancer, cancer
therapy, erwinase, glutaminase, glutamine, glutamine synthetase, immune
response, L-Asparaginase, metabolic therapy, mTOR, oncaspar, pegylation, sideeffects.
Department of Molecular Medicine, Unit of Immunology and General Pathology, University of Pavia, Via Ferrata, 9, 27100 Pavia, Italy.