Trends in Molecular Medicine
Circulating tumor cells: the ‘leukemic phase’ of solid cancers
Section snippets
Biology of circulating tumor cells
Although therapeutic advances were made during the past few decades, many patients still die from metastatic cancer despite having no clinically detectable disease after treatment. In these patients, cancer recurrence originates from microscopic tumor residues known as minimal residual disease (MRD) (see Glossary). MRD can affect different body compartments, including the bone marrow, lymph nodes and peripheral blood 1, 2, 3. The search for MRD in the peripheral blood is performed routinely for
CTC detection
Several approaches to detect CTCs have been described (Figure 2) and can be classified into PCR-based and cytometric methods. Because of the lack of comparative investigations, no ideal technique is available and many issues must be addressed when searching for CTCs.
Clinical results
Several studies have investigated the prognostic value of CTC detection in patients who have almost every type of solid malignancy (for examples, see Table 1). Because the false-positive rate among control subjects (i.e. healthy subjects or patients with non-malignant diseases) is extremely low, the specificity of both PCR-based and cytometric methods is ∼100% 23, 24. Nevertheless, because there are some conflicting results, no definitive conclusion on CTC biological significance in solid
Future perspectives
Technical and biological hurdles might prevent oncologists from proving the prognostic value of CTC detection. Several steps can be taken to address these issues and improve the quality of future studies that are designed to investigate the prognostic value of CTCs in patients with solid tumors (Table 2).
Concluding remarks
The current evidence is that malignant cells circulate in the peripheral blood of patients with solid tumors 5, 6, 7, 23. Although the results of several studies support a correlation between CTCs and patient clinical outcome, the findings of other studies question the biological significance, and thus the clinical usefulness, of CTC detection. Because the presence of CTCs is necessary (although not sufficient) for the development of metastatic-tumor spread, researchers are prompted to
Acknowledgements
We apologize to those authors whose work could not be cited owing to length restrictions.
Glossary
- β-type error:
- the statistical error (also known as type-II error) made in testing an hypothesis when it is concluded that an intervention (or prediction) is not effective (or true) but it really is.
- Cell-enrichment methods:
- any biotechnology aimed at sorting target cells (e.g. CTCs) from a pool of ‘unwanted’ cells (e.g. peripheral mononucleated cells) to increase the number of cells of interest per unit of volume (enrichment) and thus enable collection of enough biological material for molecular
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