l-Asparaginase Bio-Betters: Insight Into Current Formulations, Optimization Strategies and Future Bioengineering Frontiers in Anti-Cancer Drug Development

Cancer remains a persistent global health concern, representing a significant challenge in medical science and patient care. In this context, l-asparaginase has emerged as a promising therapeutic agent due to its unique ability to deplete circulating asparagine, thereby selectively targeting cancer cells. However, despite its potential, current formulations of l-asparaginase are not without limitations. Issues such as immunogenicity, short half-life, and variable efficacy present hurdles in its widespread clinical application. To overcome these hurdles, researchers are focusing on developing bio-better versions of l-asparaginase. These bio-betters aim to enhance stability, reduce immunogenicity, and optimize enzyme kinetics, thus improving treatment outcomes. This review critically assesses the current landscape of l-asparaginase bio-betters, offering insights into ongoing formulations and advancements, optimization strategies, and future bio-engineering frontiers. It discusses modifications to enhance therapeutic properties and explores innovative approaches like in-silico enzyme engineering and artificial intelligence, highlighting their potential to improve the therapeutic profile of l-asparaginase. Challenges and debates surrounding the l-asparaginase mechanism are also addressed. By addressing current challenges and outlining future directions, this review aims to contribute to the advancement of anti-cancer therapeutics, particularly in the context of l-asparaginase bio-better research.