Metabolic and epigenetic reprogramming in circulating tumor cells: Advances in liquid biopsy and cancer management

Circulating tumor cells are key drivers of cancer metastasis and represent powerful biomarkers for real-time monitoring of disease progression through liquid biopsy approaches. This review examines the intricate metabolic and epigenetic reprogramming that enables these cells to survive, disseminate, and resist therapy. Metabolic adaptation involves coordinated shifts in glycolysis, oxidative phosphorylation, lipid metabolism, and amino acid utilization that allow CTCs to endure oxidative stress and nutrient deprivation in the bloodstream. At the same time, epigenetic mechanisms such as DNA methylation, histone modification, and the regulation of non-coding RNAs promote plasticity, immune evasion, and metastatic competence. By integrating these molecular processes, this review presents a comprehensive understanding of how metabolic and epigenetic pathways converge to sustain tumor cell adaptability and therapeutic resistance. The discussion also highlights the latest innovations in biosensor technology, microfluidic systems, and artificial intelligence that are transforming the detection and characterization of CTCs. Furthermore, the review identifies metabolic and epigenetic vulnerabilities as promising therapeutic targets and explores emerging strategies that exploit these molecular weaknesses. Together, these insights emphasize the growing potential of circulating tumor cell-based liquid biopsies to revolutionize precision oncology and advance early detection, personalized treatment, and improved prognostic outcomes in metastatic cancer.