Recent studies have highlighted the significant role of circulating tumor DNA (ctDNA) in the management of various cancers, particularly in non-small cell lung cancer (NSCLC) and renal cell carcinoma. In a secondary analysis from the MARIPOSA trial, patients with EGFR-mutant NSCLC and detectable baseline ctDNA showed improved median progression-free survival (mPFS) when treated with amivantamab plus lazertinib compared to osimertinib, with mPFS of 20.3 months versus 14.8 months (HR 0.68, P = 0.002) (ref: Felip doi.org/10.1016/j.annonc.2024.05.541/). Similarly, the BFAST trial demonstrated the efficacy of entrectinib in ROS1-positive NSCLC, reinforcing the clinical utility of liquid biopsies for identifying targetable alterations (ref: Peters doi.org/10.1038/s41591-024-03008-4/). Furthermore, a study on donor-derived cell-free DNA (dd-cfDNA) in kidney transplant recipients indicated its potential for detecting allograft rejection, although its clinical value remains to be fully established (ref: Aubert doi.org/10.1038/s41591-024-03087-3/). The integration of ctDNA analysis into clinical practice is becoming increasingly important, as it offers a less invasive diagnostic method with faster turnaround times, facilitating timely clinical decisions in advanced cancer settings. In addition to NSCLC, ctDNA applications extend to other malignancies, including breast cancer and esophageal cancer. A study involving 292 patients with advanced breast cancer found that baseline levels of circulating tumor cells (CTCs) and ctDNA could predict clinical outcomes, with higher CTC-cluster counts correlating with worse progression-free survival (ref: Zhang doi.org/10.1158/1078-0432.CCR-24-0535/). Moreover, a novel methylation assay for esophageal cancer demonstrated high diagnostic accuracy, indicating its potential for non-invasive early detection (ref: Bian doi.org/10.1186/s13045-024-01565-2/). The ability to monitor disease status through personalized ctDNA assays in head and neck squamous cell carcinoma further emphasizes the versatility of liquid biopsy techniques (ref: Hanna doi.org/10.1158/1078-0432.CCR-24-0590/). Overall, the advancements in ctDNA and liquid biopsy technologies are paving the way for more personalized and effective cancer management strategies.