In collaboration with the Massachusetts Institute of Technology (MIT) Departments for Biological and Mechanical Engineering, the Belfer Center for Applied Cancer Science, and the Brigham and Women’s Hospital’s Pathology Department, we develop novel complementary approaches to predict patients’ responses to targeted therapies and therapeutic combinations.
The primary objective is to arrive at a treatment rationale well before the necessary information becomes available from standard diagnostic methods, such as fluorescence in situ hybridization, immunohistochemistry, or next-generation sequencing.
Flow cytometry high-throughput screening and IncuCyte imaging of apoptosis
Freshly isolated patient-derived cancer cells are subjected to a variety of driver-specific small molecules and drug combinations intended to selectively kill cancer cells, while sparing normal cells. Careful selection of the appropriate drug panel to be tested is based on the anticipated genotypic and phenotypic signatures of the a patient’s tumor, with the patient’s medical and treatment history in mind.
IncuCyte technology is then used to follow the drug-treated cancer cells in real time, and their response to the various drug treatments is determined based on their apoptotic rate and growth arrest.
Short-term treated cells are scanned via flow cytometry in a high-throughput format to detect selective drug-induced cell death.
Suspended Microchannel Resonator (SMR)
By utilizing the mass-position dependence of cantilever resonant frequencies, the SMR enables highly sensitive mass measurements of live cells at sub-picogram resolutions. Serial devices designed to successively measure cellular mass provide estimates of single cell growth rates in response to targeted therapy.
In collaboration with Dr. Scott Manalis's lab at MIT, we aim to explore the diagnostic potential of using these biophysical markers in understanding and addressing the problems of clinical drug resistance in non-small cell lung cancer (NSCLC). As with the IncuCyte approach, this technology is being developed using freshly isolated patient-derived cancer cells that are subjected to a variety of driver-specific small molecules and drug combinations.
Tumor slice cultures/drug testing
Patient biopsy cultures represent yet another angle from which we can predict patients’ response to treatment. Small pieces of the a tumor are incubated with a selected panel of drugs and subsequently assessed for drug-induced cell death by high-throughput confocal microscopy (IN Cell Analyzer).