title: Liquid biopsy and therapeutic response: Circulating tumor cell cultures for evaluation of anticancer treatment.
abstract: The lack of a robust anticancer drug screening system to monitor patients during treatment delays realization of personalized treatment. We demonstrate an efficient approach to evaluate drug response using patient-derived circulating tumor cell (CTC) cultures obtained from liquid biopsy. Custom microfabricated tapered microwells were integrated with microfluidics to allow robust formation of CTC clusters without pre-enrichment and subsequent drug screening in situ. Rapid feedback after 2 weeks promotes immediate intervention upon detection of drug resistance or tolerance. The procedure was clinically validated with blood samples (n = 73) from 55 patients with early-stage, newly diagnosed, locally advanced, or refractory metastatic breast cancer. Twenty-four of these samples were used for drug evaluation. Cluster formation potential correlated inversely with increased drug concentration and therapeutic treatment. This new and robust liquid biopsy technique can potentially evaluate patient prognosis with CTC clusters during treatment and provide a noninvasive and inexpensive assessment that can guide drug discovery development or therapeutic choices for personalized treatment.
authors.affiliation: BioSystems and Micromechanics (BioSyM) IRG, Singapore-MIT Alliance for Research and Technology (SMART) Centre, Singapore 138602, Singapore.
authors.forename: Bee Luan
authors.initials: BL
authors.lastname: Khoo
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
authors.forename: Gianluca
authors.identifier: 0000-0001-9313-6748
authors.initials: G
authors.lastname: Grenci
authors.affiliation: BioSystems and Micromechanics (BioSyM) IRG, Singapore-MIT Alliance for Research and Technology (SMART) Centre, Singapore 138602, Singapore.; Department of Biomedical Engineering, National University of Singapore, 7 Engineering Drive 1, Singapore 117574, Singapore.
authors.forename: Tengyang
authors.initials: T
authors.lastname: Jing
authors.affiliation: Department of Biomedical Engineering, National University of Singapore, 7 Engineering Drive 1, Singapore 117574, Singapore.
authors.forename: Ying Bena
authors.initials: YB
authors.lastname: Lim
authors.affiliation: Department of Hematology-Oncology, National University Cancer Institute, National University Hospital, Singapore 119074, Singapore.; Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
authors.forename: Soo Chin
authors.initials: SC
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
authors.forename: Jean Paul
authors.identifier: 0000-0003-0478-5020
authors.initials: JP
authors.lastname: Thiery
authors.affiliation: BioSystems and Micromechanics (BioSyM) IRG, Singapore-MIT Alliance for Research and Technology (SMART) Centre, Singapore 138602, Singapore.; Department of Electrical Engineering and Computer Science and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Jongyoon
authors.initials: J
authors.lastname: Han
authors.affiliation: BioSystems and Micromechanics (BioSyM) IRG, Singapore-MIT Alliance for Research and Technology (SMART) Centre, Singapore 138602, Singapore.; Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.; Department of Biomedical Engineering, National University of Singapore, 7 Engineering Drive 1, Singapore 117574, Singapore.; Department of Mechanical Engineering, National University of Singapore, Singapore 117575, Singapore.
authors.forename: Chwee Teck
authors.initials: CT
authors.lastname: Lim
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D001706:Biopsy; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D018929:Cell Culture Techniques; D004317:Doxorubicin / Q000633:toxicity; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D061986:MCF-7 Cells; D046210:Microfluidic Analytical Techniques; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000187:drug effects*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin
keywords: Breast cancer; circulating tumor cells; combinational therapy; drug response; microfluidics