Multiplexed Live-Cell Imaging for Drug Responses in Patient-Derived Organoid Models of Cancer

We apply patient derived organoid models, which are created from actual patient tumor specimens to examine how the tumors respond to drugs. We can also define the molecular characteristics that correlate with response. These results are then used to prioritize the best new therapies to advance in the clinical trials in the future.

One of the main challenges in using patient derived organoid models is that they are a finite resource. In addition, there are very few off the shelf kits to assess drug response in organoid models that preserve the sample in a format that allows for other downstream analyses, such as transcriptomic profiling. We developed a multiplexed approach to kinetically monitor therapeutic response in organoid models.

We use fluorescent dyes that are specific to different cellular processes, which provides insight into the mechanism of drug activity in each organoid model. In a single experiment we collect both functional and time course data and the samples are available for other assays. This method can be applied to assess response to a broad range of therapeutic modalities beyond small molecule inhibitors, including radiation sensitivity.

We are also continuing to innovate by developing tools for other cellular phenotypes that can be kinetically measured, such as senescence.