<scp>l</scp>‐Asparaginase Bio‐Betters: Insight Into Current Formulations, Optimization Strategies and Future Bioengineering Frontiers in Anti‐Cancer Drug Development

Abstract 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.