Ecology of PDAC Therapeutic Resistance / Disease Persistence
The PDAC tumor represents a complex ecosystem of, not only the malignant ‘species’, but also normal components including immune, mesenchymal, and endothelial cells in addition to non-cellular stromal components. To better understand the complex interactions between these various components and how they contribute to clinical outcomes, we are studying digitized whole slide images (WSI) from hematoxylin & eosin (H&E) slides derived from PDAC surgical specimens. Using a deep learning model, nuclear segmentation is performed facilitating downstream spatial analyses.
Evolutionary Therapy for PDAC
Emergence of therapeutic resistance is the proximate cause of patient death with those with PDAC. Current standard practice involves administering chemotherapy combinations at regular doses and intervals while effective and tolerable. This, in turn, eradicates sensitive cancer cells, allowing for emergence of drug-resistant disease. To study alternative dosing strategies, evolutionary therapy, we developed an orthotopic syngeneic xenograft mouse model with DNA barcoding of the tumors to allow for longitudinal measurement of clonal dynamics.
Biomarker Discovery to Monitor PDAC Dynamics
To successfully translate evolutionary therapy into the clinic, there is a critical need for non-invasive biomarkers that can facilitate measurements of PDAC disease dynamics over the course of treatment. Thus, we developed a biorepository of plasma derived from longitudinal peripheral blood samples of patients with PDAC over the course of various treatments.