Abstract

Mixed-Scale Fluidic System: Searching for Drug-induced DNA Damage in Circulating Tumor Cells

Steve Soper, Foundation Distinguished Professor; Director, Center of BioModular Multi-scale System for Precision Medicine, Adjunct Professor, Ulsan National Institute of Science & Technology, The University of Kansas

Improved therapies that yield more cures and better overall survival for cancer patients are needed. For example, women with breast cancer have a 5-year survival rate of 22% (Stage IV) and 72% (Stage III). Doxorubicin, cisplatin, paclitaxel, and tamoxifen are examples of drugs used for treating breast cancer with selection of therapy typically based on the classification and staging of the patient’s cancer. While treatment regimens assigned to some patients may be optimal using the current classification model, others within certain breast cancer sub-types fail therapy. New assays must be developed to determine how a patient’s physiology and genetic makeup affects drug efficacy. In this presentation, a series of chips are used for the isolation and processing of circulating tumor cells (CTCs). The chips quantify response to therapy using three pieces of information secured from the CTCs; (1) CTC number; (2) CTC viability; and (3) the frequency of DNA damage (abasic (AP) sites) in genomic DNA (gDNA) harvested from the CTCs. Microscale chips are used for CTC selection, CTC enumeration and viability determinations. The chip to read AP sites is a nanosensor chip made via nano-imprinting in plastics and contains a nanochannel with dimensions less than the persistence length of double-stranded DNA (~50 nm). Labeling AP sites with fluorescent dyes and stretching the gDNA in the nanochannel to near its full contour length allows for the direct readout of the AP sites, even from a single CTC. This information is used to determine how a patient is responding to therapy.