Evaluating the Biological Characteristics and Clinical Significance of Circulating Tumor Stem Cells in Cancer Progression

Circulating tumor cells (CTCs) as emerging biomarkers and CTC enumeration have been reported a correlation with disease progression and survival in metastatic cancer and reflected treatment response. The cancer stem cell characteristics of circulating tumor cells are considered to have the potential to guide treatment strategies. Expansion of the limited numbers of CTCs from a patient sample could develop personal drugs response testing and drug discovery platform. Small cell lung cancer (SCLC) represents 13% of all newly diagnosed lung cancer and is one of the most aggressive malignancies with early development of widespread metastases. The prognosis of SCLC remains dismal with a median overall survival of 10 months and a 5-year survival rate at 5%. Despite an initial response to chemotherapy, the mainstay of treatment for SCLC, drug resistance with a high relapse rate is the major cause contributing to treatment failure. The main obstacle to clarify SCLC biology and discover druggable targets are the rarity of sufficient tumor tissue from surgical resection or serial biopsies owing to its early dissemination nature. Therefore, characterization of CTCs can possibly provide clues to understanding the of SCLC. This study will collect CTC samples along treatment courses, measure the "quantity" and "quality" of CTC biological phenotypes, analyze their correlation to progression free survival and develop CTCs-based drug screening platform. The experimental designs of this study are as follows: (1) Examination of the correlation among CTCs enumeration, molecular and cancer stemness status and clinicopathological features of the disease. (2) Establish short-term expansion of CTCs method (3) Identify potential novel therapeutic compounds or drugs and personalized CTCs-based drug screening platform. We expect identify CTCs stemness biomarkers, establish CTC expansion and personalized CTCs drug screening platform will be invaluable tools for in the biomedical sciences and provide a knowledge base for further clinical applications.