CTCs represent tumor cells that have left the primary tumor and are also likely to be derived from Selleckchem CH5424802 metastases, so there is growing interest in monitoring CTC as cellular surrogates of metastatic dissemination [170]. DTCs are much less accessible than CTCs, and can be less informative [171]. While CTCs can be detected in the blood of patients with many types of solid cancer, they are best characterized in breast cancer patients and most of our knowledge on CTCs is derived from breast cancer [172] and [173]. Strong evidence indicates that the number of CTC before treatment is an independent predictor
of progression-free survival and overall survival in patients with metastatic breast [174] or prostate [175] cancers. Subsequently it has been shown that detection of even rare CTCs is associated with an increased risk of metastatic progression and reduced
survival in newly diagnosed breast cancers [176] and [177]. A clinical challenge here is to define whether CTC can be developed as reliable surrogate marker of relapse PCI-32765 purchase and progression to metastasis for individual patients with primary breast cancer undergoing adjuvant treatments. Several clinical trials are currently addressing this question [173]. Another equally challenging and relevant issue relates to the potential clinical use of CTC as biomarker to predict response to therapy in metastatic cancers. Initial evidence indicates that this might be the case in breast cancer, as persisting elevated counts of CTC during therapy predicts shorter progression-free survival and precedes radiological signs of progression [178]. Additional studies are in progress [173]. While cumulating evidence indicates that CTC counts have prognostic
and predictive clinical significance, many important questions on the biology of CTCs remain unanswered. For example, what is the best method to detect CTCs? CTCs are rare in the peripheral blood (ranging from one to hundreds of cells per ml) and reliable detection/isolation is still Galactokinase challenging [179]. Available methods are mostly based on immunomagnetic isolation using antibodies directed against the epithelial cell surface molecule EpCAM (such as the commercially available and FDA-approved system CellSearch®), followed by immunocytochemistry staining for epithelial markers (e.g. CK 8, 18, 19) [173]. As some CTCs undergo EMT, this approach may miss an important CTC subpopulation. Similar arguments also apply to the analysis of DTCs. Thus, novel enrichment strategies including EMT markers need to be developed. A second crucial question is whether all detected CTCs are potentially able to colonize distant organs and form metastases.
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