Recent developments in l-asparaginase discovery and its potential as anticancer agent

- l-Asparaginase kills asparagine dependent leukaemia cells by hydrolysing asparagine.
- Bacterial l-asparaginase is used for treatment of leukaemia and other blood cancer.
- Bacterial l-asparaginase is associated with several adverse reactions.
- These adverse reactions necessitate development of l-asparaginase from other sources.

l-Asparaginase (EC3.5.1.1) is an enzyme, which is used for treatment of acute lymphoblastic leukaemia (ALL) and other related blood cancers from a long time. This enzyme selectively hydrolyzes the extracellular amino acid l-asparagine into l-aspartate and ammonia, leading to nutritional deficiencies, protein synthesis inhibition, and ultimately death of lymphoblastic cells by apoptosis. Currently, bacterial asparaginases are used for treatment purpose but offers scepticism due to a number of toxicities, including thrombosis, pancreatitis, hyperglycemia, and hepatotoxicity. Resistance towards bacterial asparaginase is another major disadvantage during cancer management. This situation attracted attention of researchers towards alternative sources of l-asparaginase, including plants and fungi. Present article discusses about potential of l-asparaginase as an anticancer agent, its mechanism of action, and adverse effects related to current asparaginase formulations. This article also provides an outlook for recent developments in l-asparaginase discovery from alternative sources and their potential as a less toxic alternative to current formulations.