Target enzymes in serine‐glycine‐one‐carbon metabolic pathway for cancer therapy

Abstract Cancer cells selectively take up exogenous serine or synthesize serine via the serine synthesis pathway for conversion into intracellular glycine and one‐carbon units for nucleotide biosynthesis. In this process, serine‐glycine metabolism and the one‐carbon cycle play vital roles, which is named serine‐glycine‐one‐carbon metabolism (SGOC). The SGOC pathway is a metabolic network crucial for tumorigenesis with unexpected complexity and clinical importance. Accumulating evidence has demonstrated that metabolic enzymes in SGOC metabolism play key roles in tumorigenesis, metastasis and resistance to therapies. In this review, we focus on the involvement of serine and glycine in the folate‐mediated one‐carbon pathway during cancer progression and highlight the pathways through which cancer cells acquire and use one‐carbon units. In addition, we discuss the recently elucidated effects of SGOC (folate cycle) metabolic enzymes in the occurrence and development of tumors and their links to drug resistance. Inhibitors of target enzymes in the SGOC pathway display promise as investigational new drug candidates for the treatment of tumors.