ABSTRACT L‐Arginine (L‐Arg), a conditionally essential and versatile amino acid, exhibits important research values in cancer biology and therapy. L‐Arg exerts antitumor effects through multiple mechanisms, of which immune regulation represents a pivotal mechanism. As a potential adjuvant for cancer therapy, L‐Arg contributes to the inhibition of malignant cell growth and enhancement of therapeutic efficacy, and it has shown potential as a predictive biomarker for immunotherapy response. Moreover, microbiota‐mediated regulation of L‐Arg and its metabolic pathways can influence tumor progression and immune response, offering new insights into cancer treatment. However, intrinsic heterogeneity across tumor types has yielded seemingly contradictory findings—elimination of L‐Arg shows remarkable efficacy in arginine‐auxotrophic tumors, whereas L‐Arg supplementation improves therapeutic outcomes in non‐auxotrophic cancers. These complexities pose challenges for the clinical application of L‐Arg and highlight the need for context‐dependent and biomarker‐guided strategies rather than uniform supplementation. Current strategies targeting L‐Arg and its metabolic pathways are under active investigation, and integrating L‐Arg modulation with other therapeutic modalities may enhance efficacy, offering novel perspectives and opportunities for exploring innovative approaches in the field of cancer therapy.
Xiao et al. (Sun,) studied this question.