Enzymes in Metabolic Anticancer Therapy

  • Maristella MaggiEmail author
  • Claudia Scotti
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1148)


Cancer treatment has greatly improved over the last 50 years, but it remains challenging in several cases. Useful therapeutic targets are normally unique peculiarities of cancer cells that distinguish them from normal cells and that can be tackled with appropriate drugs. It is now known that cell metabolism is rewired during tumorigenesis and metastasis as a consequence of oncogene activation and oncosuppressors inactivation, leading to a new cellular homeostasis typically directed towards anabolism. Because of these modifications, cells can become strongly or absolutely dependent on specific substrates, like sugars, lipids or amino acids. Cancer addictions are a relevant target for therapy, as removal of an essential substrate can lead to their selective cell-cycle arrest or even to cell death, leaving normal cells untouched. Enzymes can act as powerful agents in this respect, as demonstrated by asparaginase, which has been included in the treatment of Acute Lymphoblastic Leukemia for half a century. In this review, a short outline of cancer addictions will be provided, focusing on the main cancer amino acid dependencies described so far. Therapeutic enzymes which have been already experimented at the clinical level will be discussed, along with novel potential candidates that we propose as new promising molecules. The intrinsic limitations of their present molecular forms, along with molecular engineering solutions to explore, will also be presented.


Cancer addictions Asparaginase Glutaminase Arginine deaminase Arginase 



L-arginine decarboxylase


Arginine deiminase




Acute lymphoblastic leukaemia




Argininosuccinate lyase




Asparagine synthetase


Aspartate aminotransferases


β-aspartyl peptidase/L-asparaginase


Argininosuccinate synthase


Argininosuccinate synthetase


Activating transcription factor 4


Adenosine triphosphate


Blood brain barrier


B-cell lymphoma 2


Cysteines-mutated and PEGylated form of ARGase I


Berlin, Frankfurt, Münster




Flavin adenine dinucleotide


Focal adhesion kinase




Glutaminase C


Glycine cleavage system


Bacterial glutaminase


Mammalian glutaminase


Glycine oxidase


Erythrocytes encapsulating L-asparaginase


Kidney glutaminase


Kirsten Rat sarcoma virus


Mycoplasma arginini derived ADI




Methylthioadenosine phosphorylase


Mammalian target of rapamycin complex 1


Methionine synthase

MYC and c-MYC

Myelocytomatosis gene


Dihydronicotinamide-adenine dinucleotide Phosphate


National cancer institute-60 collection of cancer cell lines


N-terminal nucleophile


Ornithine aminotransferase


Ornithine transcarbamyl transferase




Pyrroline-5-carboxylate synthase


Plasminogen activator


Polyethylene glycole


Phosphoglycerate dehydrogenase


p53-induced gene 6


Pyrodoxal phosphate




Pseudomonas putida L-methioninase


Proline oxidase


Phosphoserine aminotransferase 1


Phosphoserine phosphatase


Proline utilization A


Pyrroline-5-carboxylate reductase


Rapidly accelerated fibrosarcoma


Rat sarcoma


Red blood cell


RNA interference


Radical oxygen species


Rous sarcoma virus-transformed buffalo-rat liver




Succinimidyl carbamate


Calaspargase pegol


Serine dehydratase


Serine hydroxymethyltransferase


L-tyrosine-2-oxoglutarate aminotransferase


Tricarboxylic acid cycle


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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Molecular Medicine, Unit of Immunology and General PathologyUniversity of PaviaPaviaItaly

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