(497e) Measurement of Cancer Cell Drug Response with Quantitative Phase Imaging

There are no biomarkers that can accurately predict chemotherapy response in advanced cancer patients and less than 10% of patients with a detected targetable mutation are eligible for a clinical trial. There is a need for new diagnostic methods that can accurately stratify high-risk patients to effective, FDA-approved therapies. Our current patient-derived models for assessing tumor drug response involve expanding patient tumor cells as 3D patient derived organoids (PDO) in Matrigel or using in vivo drug sensitivity studies with patient-derived xenograft models (PDX). These experimental models typically exhibit the same phenotype and molecular alterations in vivo and ex vivo and have the same drug responses as in the patient. However, these methods require 1-8 months to obtain drug sensitivity profiles making this impractical for patient care. We have tested a functional assay based on quantitative phase imaging (QPI) with the capability to predict cancer cell response to therapy within 24 h of data collection. QPI is a label-free microscopy method that uses light to measure the mass of single cancer cells. By tracking the mass of growing cancer cells over time, QPI provides a rapid measurement of cell growth or death that can be used to monitor response/resistance to different drug therapies. QPI also provides data on heterogeneity of response that may indicate emergence of resistant subpopulations. We have developed and validated a QPI imaging system for dedicated screening of breast cancer cell response to therapy. We validated this approach against gold standard measurements and will show response profiles to a panel of FDA-approved chemotherapies. The overall goal of our work is to provide real-time feedback to oncologists on drug sensitivity/resistance and resistant subpopulations.