Slug-positive circulating tumor cells in mesenchymal malignancies: what remains to validate

Circulating tumor cells show promise as noninvasive response biomarkers, but their utility in mesenchymal malignancies requires further validation. This commentary examines He and colleagues' study proposing Slug-positive circulating tumor cells as predictors of neoadjuvant chemotherapy response. While the study provides valuable exploratory data, three considerations warrant careful interpretation: (1) Response Evaluation Criteria in Solid Tumors criteria versus histopathological assessment, the preferred sarcoma reference standard; (2) potential Epithelial Cell Adhesion Molecule-enrichment limitations for low-EpCAM mesenchymal tumors; and (3) the need for larger validation cohorts. Further investigations incorporating sarcoma-specific endpoints, optimized circulating tumor cell platforms, and adequately powered studies are needed before clinical application.