PHGDH is a key enzyme in the serine biosynthesis pathway, playing a critical role in cancer progression, metastasis, and drug resistance. It is involved in one-carbon metabolism, contributing to DNA synthesis and antioxidant production. Elevated PHGDH activity in cancer cells is driven by genetic amplification, post-translational modifications, increased transcription, and allosteric regulation. PHGDH is essential for serine production, which supports cancer cell growth, proliferation, and survival. Its expression is correlated with tumor aggressiveness and poor prognosis in various cancers, including lung, colorectal, pancreatic, breast, and thyroid cancers. PHGDH isoforms vary among organisms, with Type I being dominant in humans and other species. PHGDH is regulated by post-translational modifications, such as acetylation, ubiquitination, and methylation, which influence its activity and function. Modulators like p300, Josephin-2, and Cofilin1 affect PHGDH expression and activity, impacting cancer progression. PHGDH is also involved in cancer drug resistance, as its inhibition can overcome resistance mechanisms and enhance the efficacy of chemotherapy. PHGDH inhibition has shown promise as a therapeutic target in various cancers. Studies have demonstrated that PHGDH inhibitors can suppress tumor growth, reduce metastasis, and improve treatment outcomes. For example, in lung, colorectal, and pancreatic cancers, PHGDH inhibition reduced tumor progression and increased survival. In breast cancer, PHGDH inhibition enhanced the effectiveness of chemotherapeutic agents like doxorubicin and erlotinib. Combining PHGDH inhibition with other therapies, such as radiotherapy or diet therapy, has shown synergistic effects in cancer treatment. However, PHGDH inhibition may have adverse effects, particularly in embryonic development, highlighting the need for careful consideration in drug development. Overall, PHGDH is a promising therapeutic target for cancer treatment, with ongoing research aimed at improving its application in various cancers.PHGDH is a key enzyme in the serine biosynthesis pathway, playing a critical role in cancer progression, metastasis, and drug resistance. It is involved in one-carbon metabolism, contributing to DNA synthesis and antioxidant production. Elevated PHGDH activity in cancer cells is driven by genetic amplification, post-translational modifications, increased transcription, and allosteric regulation. PHGDH is essential for serine production, which supports cancer cell growth, proliferation, and survival. Its expression is correlated with tumor aggressiveness and poor prognosis in various cancers, including lung, colorectal, pancreatic, breast, and thyroid cancers. PHGDH isoforms vary among organisms, with Type I being dominant in humans and other species. PHGDH is regulated by post-translational modifications, such as acetylation, ubiquitination, and methylation, which influence its activity and function. Modulators like p300, Josephin-2, and Cofilin1 affect PHGDH expression and activity, impacting cancer progression. PHGDH is also involved in cancer drug resistance, as its inhibition can overcome resistance mechanisms and enhance the efficacy of chemotherapy. PHGDH inhibition has shown promise as a therapeutic target in various cancers. Studies have demonstrated that PHGDH inhibitors can suppress tumor growth, reduce metastasis, and improve treatment outcomes. For example, in lung, colorectal, and pancreatic cancers, PHGDH inhibition reduced tumor progression and increased survival. In breast cancer, PHGDH inhibition enhanced the effectiveness of chemotherapeutic agents like doxorubicin and erlotinib. Combining PHGDH inhibition with other therapies, such as radiotherapy or diet therapy, has shown synergistic effects in cancer treatment. However, PHGDH inhibition may have adverse effects, particularly in embryonic development, highlighting the need for careful consideration in drug development. Overall, PHGDH is a promising therapeutic target for cancer treatment, with ongoing research aimed at improving its application in various cancers.