Relevance of Circulating Tumor Cells as Predictive Markers for Cancer Incidence and Relapse

Abstract

Shedding of cancer cells from the primary site or undetectable bone marrow region into the circulatory system, resulting in clinically overt metastasis or dissemination, is the hallmark of unfavorable invasive cancers. The shed cells remain in circulation until they extravasate to form a secondary metastatic lesion or undergo anoikis. The circulating tumor cells (CTCs) found as single cells or clusters carry a plethora of information, are acknowledged as potential biomarkers for predicting cancer prognosis and cancer progression, and are supposed to play key roles in determining tailored therapies for advanced diseases. With the advent of novel technologies that allow the precise isolation of CTCs, more and more clinical trials are focusing on the prognostic and predictive potential of CTCs. In this review, we summarize the role of CTCs as a predictive marker for cancer incidence, relapse, and response to therapy.

Keywords: circulating tumor cells; companion diagnostics; liquid biopsy; precision medicine; predictive biomarker.

Figure 1

Significance of CTC research in clinical translation. (A) CTCs can help in screening and identifying patients who are predisposed to cancer (represented as gray zone) due to familial history, intermediated expression of cancer-associated markers (such as PSA), or other comorbidities, and thereby prevent overtreatment (overdiagnosis) or undertreatment of patients in gray zone. (B) Patient stratification based on CTC count or CTC expression of clinically targetable markers can improve patient outcomes by altering the therapeutic strategy and developing more personalized therapy decisions. (C) CTC can provide prognostic information on cancer progression or early/late recurrences in different cancer types. (D) CTCs allow for real-time monitoring at different stages of cancer treatment, and combined with conventional radiological/histological information can help in treatment decisions while being a tool for continued surveillance in the DFS period.

Figure 2

Significance of CTCs in basic research. (A) Biomarker discovery through CTC culture and CTC based in vivo models effectively enables drug screening and therapeutic drug target identification. (B) Tumor cells undergo genetically distinct subclonal and clonal expansion by therapeutic pressure, and molecular analysis of CTCs supports the development of optimal therapeutic regimens. (C) Various factors related to extravasation, enrichment, and colonization of distant organs for metastasis of CTCs have been unraveled. (D) Understanding the mechanisms of drug resistance by CTC characterization contributes to finding more suitable therapies for disease relapse.