The utilization of microfluidic technology for the clinical study of circulating tumor cells (CTCs) in the blood, and the feasibility study of its application for clinical chemotherapy drug selection

Cancer metastasis is a leading cause of cancer-derived death. During cancer progression, circulating tumor cells (CTCs), the rare cell species present in the blood, have been found in the peripheral blood not only during metastasis but also at the early stage of cancer development. CTCs are considered to mainly contribute to cancer metastasis or relapse, and thus can be an important indicator in determining the prognosis of cancer patients. Moreover, CTCs can be the therapeutic target of metastatic cancer care. Therefore, the use of viable CTCs as biopsy to select therapeutic approaches and their optimum conditions opens up a promising route to realize personalized cancer therapy. Furthermore, the responses of CTCs to therapy (e.g. drug sensitivity or resistance) can also be an indicator for monitoring the long-term therapeutic effect in a real-time and noninvasive manner. This can provide predictive information for the adjustment of therapeutic scheme through the stages of disease progression. To achieve these goals, the CTCs separated from blood sample must not only be maintained viable but also be kept their proliferative capability so as to expand cells in number for the subsequent cell-based anti-cancer drug testing. Nevertheless, the current methods for CTCs isolation/separation are mostly for CTCs detection or enumeration purposes, and thus the separated CTCs are either stained with specific dyes, or bound with magnetic beads. In these cases, the captured CTCs might not be suitable for further cell culture application. Due to the phenotypic heterogeneity of CTCs, more importantly, the risk of biased CTC isolation could occur while the current positive selection-based CTCs isolation/separation schemes are adopted, in which the clinically-meaningful CTCs associated with metastatic disease might miss. Apart from the CTCs separation issue, the in vitro culture of the CTCs based on conventional cell culture model (e.g. static and monolayer cell culture formats) has been a technical challenge. This problem could hinder the use of CTCs for the subsequent cell-based anti-cancer drug testing. Moreover, the CTCs-based anti-cancer drug testing for guiding personalized cancer therapy is still in its infancy stage. More evidences are needed to justify its clinical value. In order to address the above technical issues, this research project is proposed. Borrowing from the advantagous features of microfluidic technology, a negative selection-based CTCs separation scheme, capable of isolating the all possible CTCs in blood sample without affecting their cell viability and proliferative capability, will be proposed in the first year project. Based on our experiences on microfluidic cell culture systems, moreover, a CTCs cell culture model, in which the in vitro CTCs response to anti-cancer drug stimulation is more representative to its in vivo counterpart, will be established in the second year project. In the third year project, the clinical effectiveness of CTCs-based anti-cancer drug testing-guided chemotherapy will be evaluated.

Project ID:PB10202-1468
External Project ID:NSC101-2221-E182-001-MY3