Recent studies have highlighted the significance of circulating tumor DNA (ctDNA) in monitoring cancer progression and treatment response. In a randomized clinical trial, patients with EGFR-mutant non-small-cell lung cancer (NSCLC) were treated with osimertinib based on ctDNA T790M mutation detection, leading to a progression-free survival rate of 67.2% in the treatment group compared to 53.5% in the control group, with a median overall survival not reached versus 42.8 months, respectively (ref: Remon doi.org/10.1016/j.annonc.2023.02.012/). Additionally, a longitudinal study involving 466 NSCLC patients demonstrated that ctDNA dynamics could predict overall survival, utilizing machine learning to analyze multiple ctDNA metrics across five time points (ref: Assaf doi.org/10.1038/s41591-023-02226-6/). These findings underscore the potential of ctDNA as a biomarker for personalized treatment strategies, although challenges remain in standardizing ctDNA monitoring protocols across diverse patient populations. Moreover, the role of mitochondrial DNA mutations in myelodysplastic syndromes (MDS) post-stem cell transplantation was explored through whole-genome sequencing of 494 patients, revealing that mtDNA mutations significantly impacted overall survival and transplant-related mortality (ref: Dong doi.org/10.1186/s13045-023-01418-4/). This study emphasizes the need for comprehensive genomic profiling in cancer management, as mtDNA alterations could serve as critical prognostic indicators in MDS patients.