Clinical Relevance of Mutational Detection for High-Purity Circulating Tumor Cells from Cancer Patients with Disruptive Gene Mutation(S)

Distant metastasis of cancer remains the major cause of cancer death. One of the evidence is that some rare cells shed from primary tumor exist in the circulation of cancer patients, which has been proven to be related to cancer relapse and distant metastasis. The number of circulating tumor cells (CTCs) or the expression status of specific marker(s) on them also correlated with the disease prognosis and treatment effects, which might change the decision of treatments. In recent years, as specific disruptive genes were discovered, such as EGFR in non-small cell lung cancer, KRAS in colorectal cancer, the response rate to treatment, disease control and survival have been much improved. However, the molecular information obtained from cancer tissue depends on repeated biopsies, which is very risky and invasive to cancer patients. By means of the advances of CTCs sampling technique with genetic analysis, repeated follow-up for specific gene profiles is possible. However, the protocol has not been well-established and mature, even the correlation between primary cancer tissue and CTCs remains unknown. To tackle the problems above, the aims of the project is to isolate high-purity CTCs by the optically induced dielectrophoresis (ODEP)-based device or other cell sorting techniques and transfer to next-generation sequencing (NGS) analysis for specific disruptive genes. In the first year of the project, we will testify and stabilize the platform utilizing healthy donors' blood and cancer cell lines and adjust the detailed experiment conditions. In the following years(2nd and 3rd), we will enroll newly diagnosed metastatic cancer patients with the disruptive gene mutation(s) and follow up the events under gene-based therapy. Comparison of NGS information between cancer tissue and CTCs will be also made as one of the major endpoints. In brief, we expect the study could establish a practical method to get genetic information, to reduce the risk of re-biopsy and to achieve the ultimate goal of precision medicine.Keywords: Circulating tumor cells (CTCs), Optically induced dielectrophoresis (ODEP), cell sorting, next-generation sequencing, disruptive mutation.

Project ID:PC10708-0729
External Project ID:MOST107-2314-B182-053