Simple Summary

Circulating tumor cells (CTCs), 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 CTC 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 over expression 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

the 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.