Growing evidence suggests that analysis of circulating tumor cells (CTC) or circulating tumor DNA (ctDNA) can provide a comprehensive real-time picture of the tumor-associated changes in an individual cancer patient and might address both spatial and temporal heterogeneity of cancer. The prognostic and predictive ability of the combination of both biomarkers may yield complementary information and thereby improve diagnostic sensitivity. CTC are shed by a primary tumor into the blood stream of cancer patients, and their number is correlated to prognosis. To date, the CellSearch is the only CTC test cleared by FDA for monitoring of metastatic cancer patients. The system detects CTC from whole blood of cancer patients through an immunomagnetic selection using a suspension of magnetic nanoparticles conjugated to a mouse monoclonal antibody recognizing the EpCAM present on surface of epithelial origin cells. Nevertheless, in the following years several studies have demonstrated that a mixture of EpCAM-positive and EpCAM-negative tumor cells circulate in the blood of cancer patients. Therefore, an unsolved question is the frequency, the molecular characteristics and the clinical relevance of those CTC which do not express EpCAM and are thus currently not detected by the CellSearch.
The use of ctDNA as a clinical response marker for cancer patients has already moved into the clinical routine and mutational analysis from plasma has been proven to complement tissue-based testing in many cancer types.
Aim of this proposal is to compare the genetic information provided by EpCAM-positive, EpCAM-negative and plasma ctDNA from a single blood draw in order to understand the predictive value of each liquid biopsy source in longitudinal monitoring of targeted therapies.
