Cell Circuits and Epigenomics Program Seminar Series

Address to event

The Broad Institute, 415M-CR Monadnock Room (2040)
415 Main Street,
Cambridge, MA

David Weinstock, MD (DFCI), Scott Manalis, PhD (Biological and Mechanical Engineering MIT), and Keith Ligon, MD, PhD (DFCI)

Precise measurement of single cancer cell mass accumulation to characterize drug susceptibility

Approaches to functionally measure cell response to cancer therapies could greatly aid drug selection for individual patients. However, no functional assays are currently implemented clinically, and predictive genetic biomarkers are available for only a small fraction of cancer therapies. We will describe efforts underway in the Manalis, Ligon, and Weinstock laboratories that utilize iterative measurements of single-cell mass over a 15-minute interval to quantify the effects of drug incubation on “instantaneous growth rates (iGR)” and show that changes in iGR accurately reflect drug sensitivity in single cells. Profiles of iGR reveal heterogeneity both within and across individual tumors and tumor types. When determined after several hours of ex vivo drug incubation, iGRs predict sensitivity or resistance of glioblastoma patient-derived cell lines and primary leukemias targeted inhibitors. Compatibility with downstream characterization is maintained since sensitivity is de termined without compromising cell viability. These unique capabilities of iGR measurement establish it as a promising ex vivo approach for directly assaying single-cell therapeutic response to identify subpopulations with phenotypic resistance within heterogeneous tumors.