Fluid biopsy for solid tumors: a patient's companion for lifelong characterization of their disease

Abstract

Cancer is currently diagnosed and treated based on the results of a tissue biopsy of the primary tumor or a metastasis using invasive techniques such as surgical resection or needle biopsy. New technology for retrieving cancer cells from the circulation, developed in the last 5 years, has made it possible to obtain a 'fluid biopsy' from the bloodstream without the need for an invasive procedure. This technological development makes it possible to diagnose and manage cancer from a blood test rather than from a traditional biopsy. It also allows the repeated sampling of cancer cells from a patient, making it possible, in a practical manner, to interrogate the disease repeatedly in order to understand the mechanisms by which cancer cells evolve within a given individual. The ability to obtain cancer cells repeatedly also has the potential to substantially advance drug development by enabling early ex vivo validation of both targets and early-stage compounds, as well as creating new efficiencies in the drug development process during clinical trials.

Figure 1. Historical medical journal article by Thomas Ashworth from 1869 describing circulating tumor cells

Figure 2. The central challenge to using single-parameter enrichment techniques in identifying rare cells

This example of computational size filtering of a single patient sample demonstrates the limitations of single-parameter enrichment. Assuming an area threshold at the 50% level (allowing for 50% false-negative rates) would result in an overwhelming number of 110,090 false-positive events. CTC: Circulating tumor cell; HD: High definition; WBC: White blood cell.

Figure 3. The CTC-chip developed at the Massachusetts General Hospital (MA, USA) uses silicone posts coated with anti-EpCAM antibodies to capture circulating tumor cells

CTC: Circulating tumor cell; NSCLC: Non-small-cell lung cancer. Reproduced with permission from [52].

Figure 4. The high-definition circulating tumor cell assay and identification process

(A) The sequence of events in a high-definition CTC assay. (B) and (C) show two high-definition CTC clusters displaying the typical high-definition CTC fluorescence patterns. CTC: Circulating tumor cell.