New opportunities and challenges for nonshedder tumors

Cancer remains a leading cause of mortality worldwide. While surgical resection effectively controls localized tumors, postoperative recurrence remains a significant challenge. Circulating tumor DNA (ctDNA), a key biomarker in liquid biopsy, has garnered considerable attention for its non-invasive nature and high specificity in monitoring cancer recurrence. However, some patients exhibit ctDNA nonshedding characteristics before surgery, and the underlying mechanisms remain unclear. This review examines the distinctive features of nonshedder tumors, highlighting the influence of tumor stage, metabolic activity, genetic variation, and the tumor microenvironment on ctDNA shedding. Based on these insights, we discuss emerging opportunities and challenges associated with nonshedder tumors and propose directions for future research.