Current progress in the clinical use of circulating tumor cells as prognostic biomarkers

Abstract

The process of metastasis is characterized by the shedding of tumor cells into the bloodstream, where they are transported to other parts of the body to seed new tumors. These cells, known as circulating tumor cells (CTCs), have the potential to reveal much about an individual cancer case, and theoretically can aid in the prediction of outcomes and design of precision treatments. Recent advances in technology now allow for the robust and reproducible characterization of CTCs from a simple blood draw. Both the number of circulating cells and important molecular characteristics correlated with clinical phenotypes such as drug resistance can be obtained and used for real‐time prognostic analysis. Molecular characterization can provide a snapshot of the activity of the main tumor (serving as a “liquid biopsy”) and early warnings concerning changes such as the development of resistance, and aid in predicting the efficacy of different therapeutic approaches for treatment optimization. Herein, the authors review the current clinical use of CTCs as prognostic biomarkers for several different cancers. The quantification of CTCs can lead to more accurate staging and decision making regarding options such as adjuvant chemotherapy.

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“…Alteration of epigenetic pathways and changes in the tumor microenvironment is an emerging mechanism to initiate pancreatic cancer metastasis [4]. In addition, the shedding pancreatic cancer cells, also known as circulating tumor cells (CTCs), from the primary focus can enter into the bloodstream and transport to other parts of the body to seed new tumors [5].…”

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“…In the era of precision medicine, accurate prognostication helps guide the selection of appropriate and effective treatment strategies [ 66 ]. Thus, many studies have aimed to develop prognostic models to predict outcomes in PDAC [ 67 – 69 ].…”

EV Translational Horizons as Viewed Across the Complex Landscape of Liquid Biopsies

“…Such CTC assays, especially assays that combine tests for tumor-associated surface proteins with tests for tumor-specific genetic mutations, have been shown to predict treatment responses and improve treatment selection for several types of cancers ( Autio et al, 2014 ; Dittamore et al, 2014 ; Scher et al, 2016 , 2017 ; Lack et al, 2017 ; Figueroa and Carter, 2018 ; Armstrong et al, 2019 ; Salami et al, 2019 ). However, CTCs circulate in low concentrations, typically at levels of 1–10 CTCs per milliliter of blood, and some types of tumors are associated with lower levels of CTCs than others, so, for many types of tumors, it can be difficult to capture a full range of tumor heterogeneity in CTCs from standard blood sample volume ( Figueroa and Carter, 2018 ; Jin et al, 2019 ).…”