Serine Metabolic Reprogramming in Tumorigenesis, Tumor Immunity, and Clinical Treatment

Serine has been recently identified as an essential metabolite for oncogenesis, progression, and adaptive immunity. Influenced by many physiologic or tumor environmental factors, the metabolic pathways of serine synthesis, uptake, and usage are heterogeneously reprogrammed and frequently amplified in tumor or tumor-associated cells. The hyperactivation of serine metabolism promotes abnormal cellular nucleotide/protein/lipid synthesis, mitochondrial function, and epigenetic modifications, which drive malignant transformation, unlimited proliferation, metastasis, immunosuppression, and drug resistance of tumor cells. Dietary restriction of serine or phosphoglycerate dehydrogenase depletion mitigates tumor growth and extends the survival of tumor patients. Correspondingly, these findings triggered a boom in the development of novel therapeutic agents targeting serine metabolism. In this study, recent discoveries in the underlying mechanism and cellular function of serine metabolic reprogramming are summarized. The vital role of serine metabolism in oncogenesis, tumor stemness, tumor immunity, and therapeutic resistance is outlined. Finally, some potential tumor therapeutic concepts, strategies, and limitations of targeting the serine metabolic pathway are described in detail. Taken together, this review underscores the importance of serine metabolic reprogramming in tumorigenesis and progression and highlights new opportunities for dietary restriction or selective pharmacologic intervention.