L-arginine metabolism in breast cancer: mechanisms and therapeutic targets

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related death among women worldwide. It is a highly heterogeneous disease that can be divided into different molecular subtypes, which differ in morphology, prognosis, and treatment response. While metabolic reprogramming is known to support tumor growth and survival, the specific role of L-arginine metabolism in breast cancer is not completely understood. L-Arginine is a semi-essential amino acid, it is involved in key pathways regulating cell proliferation, immune response, and protein metabolism. Dysregulation of L-arginine-related enzymes, such as arginases and nitric oxide synthases, can influence tumor growth, metabolic signaling, and the interaction between cancer and immune cells. Therapeutic targeting of L-arginine metabolism has been explored by three main approaches: L-arginine starvation, L-arginine supplementation, and enzyme inhibition. However, results have remained inconsistent, possibly due to differences in metabolic adaptations across molecular breast cancer subtypes. This review provides an overview of current knowledge on L-arginine metabolism in breast cancer, including metabolic reprogramming, subtype-specific regulation, and therapeutic opportunities. It also discusses challenges and highlights the need for further research to define subtype-specific regulation of L-arginine metabolism.