Metabolic differences between normal and cancerous cells have been used as a point of view for developing anticancer drugs. Deprivation of the specific amino acids using degradation enzymes has been regarded to kill cancerous cells. L-Asparaginase (ASNase) has shown an excellent therapeutic response to some asparagine-auxotrophic cancers, such as acute lymphoblastic leukemia (ALL). Some bacteria, yeasts, molds, plants, and animals produce ASNase. Bacterial ASNase from Escherichia coli and Erwinia chrysanthemi is the FDA-approved drugs for ALL treatment. Here, we review recent advances to introduce new natural prokaryotic and eukaryotic sources of ASNase and improvement strategies in the production of recombinant ASNase, its chemical modifications, in silico studies, immobilization, and nanoencapsulation to increase its efficiency and decrease its side-effects. Some recent studies in the application of ASNase in the treatment of asparagine-auxotrophic cancers, especially solid cancers, have been reviewed. Furthermore, challenges and suggestions/opinions are discussed for this promising therapeutic enzyme.
