(137f) Longitudinal Tracking of Single Cells Reveals Drug Resistant Phenotypes in Cancer

Understanding the mechanisms of drug resistance is one of the major challenges in the field of cancer biology, demanding the development of improved methods to characterize the drug resistant phenotypes present in cancer cells. Current methods for evaluation of drug resistance use bulk dose-response assays masking the heterogeneity inherently present in the response of individual cancer cells. Here, we present a novel microfluidic method for characterizing the drug response of individual cells by longitudinally tracking their proliferation capacity across several generations. We simultaneously monitor more than 1000 single breast cancer cells exposed to the chemotherapy drug doxorubicin, and find that the surviving cells can exist in two states - proliferate by multiple cell division events or remain non-proliferative but viable. The fraction of cells showing these new drug resistant phenotypes is found to decrease with increase in doxorubicin concentration. To increase the depth of phenotyping, we use additional markers and evaluate whether the non-proliferative cells are quiescent or senescent or dormant. Finally, we determine the relationship between cell metastatic potential and the drug resistant phenotypes.