Circulating Tumor Cell (CTC) analysis is a promising new diagnostic field for cancer patients towards the estimation of risk for metastatic relapse or metastatic progression. In contrast to tumor biopsies, peripheral blood samples can be frequently and sequentially obtained for CTC isolation and downstream analysis. The non-invasive isolation of CTCs from peripheral blood and their further downstream molecular characterization at the protein, DNA and RNA level, could now serve as a "liquid biopsy" approach and eventually offer additional information and even more a serious advantage over the conventional and well established tumor biopsy approach. Cell free DNA (cfDNA) circulating in plasma or serum of cancer patients has also been recently proposed as an alternative to CTCs liquid biopsy approach. It has been recently shown that by using extremely powerful and highly sensitive detection techniques, the presence of specific mutations in plasma of cancer patients could give valuable information concerning response to specific molecular targeted therapies. However, there is a substantial difference between these two approaches; CTCs are viable cells, circulating in blood, and understanding their biology in a holistic way, could give valuable information on the metastatic spread, elucidate their connection to cancer stem cells, and reveal active and possible targetable signaling networks, while cfDNA can give specific information as a circulating biomarker, for the presence or absence of specific alterations indicating therapy response. 

Different analytical systems for CTCs isolation and detection have been developed most including separation steps by size or biological characteristics such as expression of epithelial or cancer-specific markers. Recent technical advancements in CTCs detection and characterization include multiplex RT-qPCR based methods, image-based approaches and microfilter and microchip devices. New areas of research are directed toward developing novel sensitive assays for CTCs molecular characterization. Quality control is an important issue for the clinical use of CTCs analysis, and standardization of micrometastatic cell detection and characterization methodologies is important for the incorporation of CTCs into prospective clinical trials testing their clinical utility. The molecular characterization of CTCs can provide important information on the molecular and biologic nature of these cells such as the status of hormone receptors, epidermal, and other growth factor receptor family members and indications of stem-cell characteristics. This is very important for the identification of therapeutic targets and resistance mechanisms in CTCs as well as for the stratification of patients and real-time monitoring of systemic therapies. 

ACTC lab main interests

Our lab is specializing on the development, analytical validation and clinical evaluation of molecular assays for the detection, enumeration and molecular characterization of CTCs.

More specifically, our  main research interests are on:

• study of micrometastasis through the development of singleplex and multiplex quantitative real time RT-qPCR assays for the detection of CTCs,
• development and clinical evaluation of DNA methylation assays in fresh tissues, paraffin-embedded breast carcinomas, in CTCs and in cell-free circulating DNA,
• development and clinical evaluation of quantitative real time RT-qPCR assays for the detection of mature micro RNAs in fresh tissues, paraffin-embedded breast carcinomas and in cell-free circulating DNA,
• development and clinical evaluation of highly sensitive assays for mutation analysis in CTCs and in cell-free circulating DNA,
• development and clinical evaluation of multiplex assays for gene expression in CTCs based on the Luminex bead array system.