Glutamine Supplementation as an Anticancer Strategy: A Potential Therapeutic Alternative to the Convention

Simple Summary Glutamine, vital for the body's functions, is pivotal in cancer metabolism as it influences tumor growth. However, cancer cells' complex adaptive metabolic dynamics raise concerns about potential limitations in glutamine antagonism strategies to impede tumor growth. Similarly, while glutamine supplementation shows promise in supporting cancer patients, careful considerations are necessary to address possible interactions with ongoing treatments and concerns about inadvertent tumor growth stimulation. Recent studies have shed light on the effects of glutamine on the epigenetic regulation of cancer cells and the enhancement of anti-cancer immune functions, providing valuable insights for potential therapeutic advancements. Understanding the intricacies and challenges of glutamine interventions is essential for optimizing their potential benefits in cancer treatment and patient well-being.Abstract Glutamine, a multifaceted nonessential/conditionally essential amino acid integral to cellular metabolism and immune function, holds pivotal importance in the landscape of cancer therapy. This review delves into the intricate dynamics surrounding both glutamine antagonism strategies and glutamine supplementation within the context of cancer treatment, emphasizing the critical role of glutamine metabolism in cancer progression and therapy. Glutamine antagonism, aiming to disrupt tumor growth by targeting critical metabolic pathways, is challenged by the adaptive nature of cancer cells and the complex metabolic microenvironment, potentially compromising its therapeutic efficacy. In contrast, glutamine supplementation supports immune function, improves gut integrity, alleviates treatment-related toxicities, and improves patient well-being. Moreover, recent studies highlighted its contributions to epigenetic regulation within cancer cells and its potential to bolster anti-cancer immune functions. However, glutamine implementation necessitates careful consideration of potential interactions with ongoing treatment regimens and the delicate equilibrium between supporting normal cellular function and promoting tumorigenesis. By critically assessing the implications of both glutamine antagonism strategies and glutamine supplementation, this review aims to offer comprehensive insights into potential therapeutic strategies targeting glutamine metabolism for effective cancer management.