• Serine metabolism is reprogrammed in multiple cancers, driven by upregulation of key enzymes (PHGDH, PSAT1, PSPH, SHMT) to support tumor growth.
• Regulation occurs at three levels: transcriptional (transcription factors, histone modifications, DNA methylation), post-transcriptional (non-coding RNAs, RNA-binding proteins, RNA modifications), and post-translational (protein modifications).
• Transcriptional and post-transcriptional mechanisms mainly control enzyme expression, while post-translational modifications modulate activity, stability, and localization.
• Targeting serine metabolic enzymes and their regulatory networks offers promising therapeutic strategies for cancer treatment.