ANALYSIS AND THERAPEUTIC TARGETING OF CIRCULATING CELLS IN METASTATIC CANCER

Abstract

Current cancer treatments, including surgery, radiotherapy and chemotherapy, have shown great success in treating solid and early metastatic tumors. Recently, investigators have examined the effects of these cancer treatment in promoting cancer metastasis. Based on recent studies, experimental evidence suggests that surgery, radiotherapy and chemotherapy induce an influx of circulating tumor cell (CTCs) into the bloodstream due to the disruption and destabilization of the tumor microenvironment. In a natural process of cancer metastasis, which is the main cause of cancer-related death, CTCs are shredded from the primary tumor into the bloodstream then seed and form macrometastases in distant organs. Once CTCs enter the blood, they face several stresses that can destroy them during transitional migration. Thereby, CTCs may travel in clusters with stromal cells, such as cancer-associated fibroblasts (CAFs), to enhance their survival in the bloodstream and improve the overgrowth of these cells in distant tissues. The scope of the work presented is divided in four sections, including: (1) A determination of the fluctuation of CTCs and CAF numbers, and the efficacy of a CTC-targeted therapy in blood samples collected from localized cancer disease undergoing prostatectomy, (2) A evaluation of the fluctuation of CTC and CAF numbers, and the efficacy of our previous mentioned therapy in blood samples collected from metastatic cancer disease undergoing chemotherapy treatment chemotherapy, (3) An investigation of the function of CAF incorporated into CTC clusters as a collective migration unit in prostate cancer progression, and (4) The development of a novel platelet-based therapy to kill CTCs with the goal of preventing metastasis.