Simple summary

Circulating tumor cells (CTCs), which are cancer cells shed from primary tumors into the bloodstream, are emerging as dynamic, non-invasive biomarkers for real-time cancer monitoring, especially when tissue biopsies are inaccessible or inadequate. Unlike static tissue samples, CTCs allow repeated assessments that track tumor evolution, therapeutic response, and minimal residual disease. Hence, CTCs offer a minimally invasive, real-time alternative to tissue biopsies for cancer monitoring, particularly through surface protein biomarkers like PD-L1, HER2, and EGFR. As detection technologies improve and the clinical relevance of CTCs continues to be established, CTC profiling is poised to significantly influence the future of precision oncology.

Abstract

Circulating tumor cells (CTCs) are shed from the primary tumor into the bloodstream and represent dynamic molecular biomarkers for monitoring the progression of cancer. While profiling tumor tissues with overexpression of cell surface markers, such as PD-L1 or HER2, is standard in guiding therapy, tissue samples are often inaccessible and inadequate, especially post-surgery or in cases of recurrence. Emerging clinical evidence indicates that CTC counts and biomarker surface expression can predict prognosis and therapeutic resistance more accurately than imaging or tissue-based approaches.

Recent advancements in CTC detection methods, based on physical properties or surface markers (e.g., EpCAM), coupled with next-generation sequencing (NGS), have enabled the isolation of these rare cells and their molecular characterization. Consequently, CTCs provide a real-time alternative, enabling repeated, longitudinal assessment of tumor phenotype and therapeutic response. This review emphasizes the translational potential of surface protein biomarkers on CTCs for profiling, namely PD-L1, HER2, and EGFR, as a clinically actionable approach to stratify patients, guide immunotherapy decisions, and monitor minimal residual disease (MRD), especially when longitudinal tissue biopsies are not feasible.