Circulating Tumor Cells as Diagnostic Tools and Therapeutic Targets

Circulating tumor cells have been a major area of focus for cancer metastasis research for the last few decades, and while the majority of progress has mainly centered on the isolation and enumeration of CTC for prognostic purposes, researchers are beginning to explore additional uses for CTC in the clinical setting. While it is well known that CTC counts correlate with prognosis, CTC counts are also being explored as a marker for response to therapy. CTC enumerated before and after surgical procedures are shedding light on the advantages of minimally invasive techniques. CTC characterization has also increased in the past decade. When CTC were first reliably isolated, the majority of work focused solely on EpCAM-expressing cells found within the blood of patients with late stage cancer. Today, EpCAM-negative CTC and CTC expressing mesenchymal markers are under great scrutiny for a potentially increased metastatic potential. Moreover, CTC that differ in protein and gene expression to the primary tumor have been found elucidating prospective issues with drug targets. CTC have been isolated and identified in patients with local tumors or even pre-cancerous lesions. Here, we present a diagnostic method that uses CTC to prescreen for drug susceptibility. This method is then used to show primary CTC sensitivity to a novel TRAIL-based immunotherapeutic targeted towards CTC. Peripheral blood samples are shown to contain circulating stromal cells believed to migrate alongside CTC and likely alter their survival under shear conditions as well as their drug susceptibility. We culminate these studies by conducting the first efficacy study of EST liposomes in an immunocompetent breast cancer tumor resection murine model