Clare, C. E., Brassington, A. H., Kwong, W. Y., & Sinclair, K. D. (2019). One-carbon metabolism: Linking nutritional biochemistry to epigenetic programming of long-term development. Annual Review of Animal Biosciences, 7, 263–287. https://doi.org/10.1146/annurev-animal-020518-115206

Article  PubMed  CAS  Google Scholar 

Yang, M., & Vousden, K. H. (2016). Serine and one-carbon metabolism in cancer. Nature Reviews Cancer, 16(10), 650–662. https://doi.org/10.1038/nrc.2016.81

Article  PubMed  CAS  Google Scholar 

Yu, W., Wang, Z., Zhang, K., Chi, Z., Xu, T., Jiang, D., et al. (2019). One-carbon metabolism supports S-Adenosylmethionine and histone methylation to drive inflammatory macrophages. Molecular Cell, 75(6), 1147-1160.e1145. https://doi.org/10.1016/j.molcel.2019.06.039

Article  PubMed  CAS  Google Scholar 

Pham, V. N., Bruemmer, K. J., Toh, J. D. W., Ge, E. J., Tenney, L., Ward, C. C., et al. (2023). Formaldehyde regulates S-adenosylmethionine biosynthesis and one-carbon metabolism. Science, 382(6670), Article eabp9201. https://doi.org/10.1126/science.abp9201

Article  PubMed  PubMed Central  CAS  Google Scholar 

Xu, D., Shao, F., Bian, X., Meng, Y., Liang, T., & Lu, Z. (2021). The evolving landscape of noncanonical functions of metabolic enzymes in cancer and other pathologies. Cell Metabolism, 33(1), 33–50. https://doi.org/10.1016/j.cmet.2020.12.015

Article  PubMed  CAS  Google Scholar 

Pan, C., Li, B., & Simon, M. C. (2021). Moonlighting functions of metabolic enzymes and metabolites in cancer. Molecular Cell, 81(18), 3760–3774. https://doi.org/10.1016/j.molcel.2021.08.031

Article  PubMed  CAS  Google Scholar 

Lee, Y., Vousden, K. H., & Hennequart, M. (2024). Cycling back to folate metabolism in cancer. Nature Cancer, 5(5), 701–715. https://doi.org/10.1038/s43018-024-00739-8

Article  PubMed  PubMed Central  CAS  Google Scholar 

Newman, A. C., Falcone, M., Huerta Uribe, A., Zhang, T., Athineos, D., Pietzke, M., et al. (2021). Immune-regulated IDO1-dependent tryptophan metabolism is source of one-carbon units for pancreatic cancer and stellate cells. Molecular Cell, 81(11), 2290-2302.e2297. https://doi.org/10.1016/j.molcel.2021.03.019

Article  PubMed  PubMed Central  CAS  Google Scholar 

Wang, J., Zeng, L., Wu, N., Liang, Y., Jin, J., Fan, M., et al. (2023). Inhibition of phosphoglycerate dehydrogenase induces ferroptosis and overcomes enzalutamide resistance in castration-resistant prostate cancer cells. Drug Resistance Updates, 70, Article 100985. https://doi.org/10.1016/j.drup.2023.100985

Article  PubMed  CAS  Google Scholar 

Shen, L., Hu, P., Zhang, Y., Ji, Z., Shan, X., Ni, L., et al. (2021). Serine metabolism antagonizes antiviral innate immunity by preventing ATP6V0d2-mediated YAP lysosomal degradation. Cell Metabolism, 33(5), 971-987.e976. https://doi.org/10.1016/j.cmet.2021.03.006

Article  PubMed  CAS  Google Scholar 

Pacold, M. E., Brimacombe, K. R., Chan, S. H., Rohde, J. M., Lewis, C. A., Swier, L. J., et al. (2016). A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate. Nature Chemical Biology, 12(6), 452–458. https://doi.org/10.1038/nchembio.2070

Article  PubMed  PubMed Central  CAS  Google Scholar 

Weinstabl, H., Treu, M., Rinnenthal, J., Zahn, S. K., Ettmayer, P., Bader, G., et al. (2019). Intracellular trapping of the selective phosphoglycerate dehydrogenase (PHGDH) inhibitor BI-4924 disrupts serine biosynthesis. Journal of Medicinal Chemistry, 62(17), 7976–7997. https://doi.org/10.1021/acs.jmedchem.9b00718

Article  PubMed  CAS  Google Scholar 

Unterlass, J. E., Baslé, A., Blackburn, T. J., Tucker, J., Cano, C., Noble, M. E. M., et al. (2018). Validating and enabling phosphoglycerate dehydrogenase (PHGDH) as a target for fragment-based drug discovery in PHGDH-amplified breast cancer. Oncotarget, 9(17), 13139–13153. https://doi.org/10.18632/oncotarget.11487

Article  PubMed  Google Scholar 

Zhao, J. Y., Feng, K. R., Wang, F., Zhang, J. W., Cheng, J. F., Lin, G. Q., et al. (2021). A retrospective overview of PHGDH and its inhibitors for regulating cancer metabolism. European Journal of Medicinal Chemistry, 217, Article 113379. https://doi.org/10.1016/j.ejmech.2021.113379

Article  PubMed  CAS  Google Scholar 

Mullarky, E., Lucki, N. C., Beheshti Zavareh, R., Anglin, J. L., Gomes, A. P., Nicolay, B. N., et al. (2016). Identification of a small molecule inhibitor of 3-phosphoglycerate dehydrogenase to target serine biosynthesis in cancers. Proceedings of the National Academy of Sciences of the United States of America, 113(7), 1778–1783. https://doi.org/10.1073/pnas.1521548113

Article  PubMed  PubMed Central  CAS  Google Scholar 

Sha, L., Wang, Y., Meng, P., Deng, Y., Chen, T., Zhang, X., et al. (2025). Pharmacological inhibition of PSPH reduces serine levels and epileptic seizures. Nature Chemical Biology. https://doi.org/10.1038/s41589-025-01920-5

Article  PubMed  Google Scholar 

Han, T., Wang, Y., Cheng, M., Hu, Q., Wan, X., Huang, M., et al. (2024). Phosphorylated SHMT2 regulates oncogenesis through m(6)a modification in lung adenocarcinoma. Advanced Science, 11(18), Article e2307834. https://doi.org/10.1002/advs.202307834

Article  PubMed  CAS  Google Scholar 

Ducker, G. S., Ghergurovich, J. M., Mainolfi, N., Suri, V., Jeong, S. K., Hsin-Jung Li, S., et al. (2017). Human SHMT inhibitors reveal defective glycine import as a targetable metabolic vulnerability of diffuse large B-cell lymphoma. Proceedings of the National Academy of Sciences of the United States of America, 114(43), 11404–11409. https://doi.org/10.1073/pnas.1706617114

Article  PubMed  PubMed Central  CAS  Google Scholar 

García-Cañaveras, J. C., Lancho, O., Ducker, G. S., Ghergurovich, J. M., Xu, X., da Silva-Diz, V., et al. (2021). SHMT inhibition is effective and synergizes with methotrexate in T-cell acute lymphoblastic leukemia. Leukemia, 35(2), 377–388. https://doi.org/10.1038/s41375-020-0845-6

Article  PubMed  CAS  Google Scholar 

Kelly, C. M., Qin, L. X., Whiting, K. A., Richards, A. L., Avutu, V., Chan, J. E., et al. (2023). A phase II study of epacadostat and pembrolizumab in patients with advanced sarcoma. Clinical Cancer Research, 29(11), 2043–2051. https://doi.org/10.1158/1078-0432.Ccr-22-3911

Article  PubMed  PubMed Central  CAS  Google Scholar 

Long, G. V., Dummer, R., Hamid, O., Gajewski, T. F., Caglevic, C., Dalle, S., et al. (2019). Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252): A phase 3, randomised, double-blind study. The Lancet Oncology, 20(8), 1083–1097. https://doi.org/10.1016/s1470-2045(19)30274-8

Article  PubMed  CAS  Google Scholar 

Reardon, D. A., Desjardins, A., Rixe, O., Cloughesy, T., Alekar, S., Williams, J. H., et al. (2020). A phase 1 study of PF-06840003, an oral indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor in patients with recurrent malignant glioma. Investigational New Drugs, 38(6), 1784–1795. https://doi.org/10.1007/s10637-020-00950-1

Article  PubMed  CAS  Google Scholar 

Kotecki, N., Vuagnat, P., O’Neil, B. H., Jalal, S., Rottey, S., Prenen, H., et al. (2021). A phase I study of an IDO-1 Inhibitor (LY3381916) as monotherapy and in combination with an anti-PD-L1 antibody (LY3300054) in patients with advanced cancer. Journal of Immunotherapy, 44(7), 264–275. https://doi.org/10.1097/cji.0000000000000368

Article  PubMed  CAS  Google Scholar 

Al-Zoubi, R. M., Elaarag, M., Al-Qudimat, A. R., Al-Hurani, E. A., Fares, Z. E., Farhan, A., et al. (2025). IDO and TDO inhibitors in cancer immunotherapy: Mechanisms, clinical development, and future directions. Frontiers in Pharmacology, 16, 1632446. https://doi.org/10.3389/fphar.2025.1632446

Article  PubMed  PubMed Central  Google Scholar 

Jung, K. H., LoRusso, P., Burris, H., Gordon, M., Bang, Y. J., Hellmann, M. D., et al. (2019). Phase I study of the indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor navoximod (GDC-0919) administered with PD-L1 inhibitor (atezolizumab) in advanced solid tumors. Clinical Cancer Research, 25(11), 3220–3228. https://doi.org/10.1158/1078-0432.Ccr-18-2740

Article  PubMed  PubMed Central  CAS  Google Scholar 

Ma, S., Suchomel, J., Yanez, E., Yost, E., Liang, X., Zhu, R., e