A retrospective overview of PHGDH and its inhibitors for regulating cancer metabolism

Abstract Emerging evidence suggests that cancer metabolism is closely associated to the serine biosynthesis pathway (SSP), in which glycolytic intermediate 3-phosphoglycerate is converted to serine through a three-step enzymatic transformation. As the rate-limiting enzyme in the first step of SSP, phosphoglycerate dehydrogenase (PHGDH) is overexpressed in various diseases, especially in cancer. Genetic knockdown or silencing of PHGDH exhibits obvious anti-tumor response both in vitro and in vivo, demonstrating that PHGDH is a promising drug target for cancer therapy. So far, several types of PHGDH inhibitors have been identified as a significant and newly emerging option for anticancer treatment. Herein, this comprehensive review summarizes the recent achievements of PHGDH, especially its critical role in cancer and the development of PHGDH inhibitors in drug discovery.