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3-Phosphoglycerate dehydrogenase: a potential target for cancer treatment

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Abstract

Background

Metabolic changes have been recognized as an important hallmark of cancer cells. Cancer cells can promote their own growth and proliferation through metabolic reprogramming. Particularly, serine metabolism has frequently been reported to be dysregulated in tumor cells. 3-Phosphoglycerate dehydrogenase (PHGDH) catalyzes the first step in the serine biosynthesis pathway and acts as a rate-limiting enzyme involved in metabolic reprogramming. PHGDH upregulation has been observed in many tumor types, and inhibition of PHGDH expression has been reported to inhibit the proliferation of PHGDH-overexpressing tumor cells, indicating that it may be utilized as a target for cancer treatment. Recently identified inhibitors targeting PHGDH have already shown effectiveness. A further in-depth analysis and concomitant development of PHGDH inhibitors will be of great value for the treatment of cancer.

Conclusions

In this review we describe in detail the role of PHGDH in various cancers and inhibitors that have recently been identified to highlight progression in cancer treatment. We also discuss the development of new drugs and treatment modalities based on PHGDH targets. Overexpression of PHGDH has been observed in melanoma, breast cancer, nasopharyngeal carcinoma, parathyroid adenoma, glioma, cervical cancer and others. PHGDH may serve as a molecular biomarker for the diagnosis, prognosis and treatment of these cancers. The design and development of novel PHGDH inhibitors may have broad implications for cancer treatment. Therapeutic strategies of PHGDH inhibitors in combination with traditional chemotherapeutic drugs may provide new perspectives for precision medicine and effective personalized treatment for cancer patients.

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Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (NSFC) [NOs. 81773594, U1803122, U1703111, 81473254, and 81773637], the National Mega-project for Innovative Drugs (grant number 2019ZX09721001-004-007), the National Science and Technology Major Project of the Ministry of Science and Technology of China (No. 2018ZX09735005), the Chunhui Program-Cooperative Research Project of the Ministry of Education, Liaoning Province Natural Science Foundation (NO. 2020-MZLH-31, 2019-MS-299) and the Liaoning Revitalization Talents Program (NO. XLYC1807182). We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.

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    1. Wuya College of Innovation, School of Pharmacy, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China

      Mingxue Li, Yueying Yang, Lixia Chen & Hua Li

    2. Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China

      Canrong Wu, Mengzhu Zheng & Hua Li

    3. Department of Medicinal Chemistry and Natural Medicine Chemistry (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, 150081, China

      Silin Yu & Jinhui Wang

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    Li, M., Wu, C., Yang, Y. et al. 3-Phosphoglycerate dehydrogenase: a potential target for cancer treatment. Cell Oncol. 44, 541–556 (2021). https://doi.org/10.1007/s13402-021-00599-9

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