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Imaging Cell-level Heterogeneity in Solid Tumors for Personalized Treatment

Imaging Cell-level Heterogeneity in Solid Tumors for Personalized Treatment


Melissa Skala, PhD
Morgridge Institute for Research
University of Wisconsin, Madison


Cancer is a complex disease that includes distinct groups of cells that are in the same tumor but react differently to treatment. This cell-to-cell diversity, or “tumor heterogeneity,” makes it difficult to eliminate all tumor cells because most drug combinations fail to kill a minority population of resistant tumor cells. These resistant tumor cells then grow and metastasize, resulting in recurrence of the disease in a more aggressive drug-resistant form. Pancreatic ductal adenocarcinoma (PDAC), which has a dismal five-year survival rate of only 7 percent, is one of the most heterogeneous cancers, resulting in significant treatment resistance. Drug development for PDAC is significantly behind that of other cancers, with no effective targeted drugs on the market. Standard-of-care chemotherapies for PDAC exhibit varying degrees of toxicity and effectiveness and there is no rational system to match each patient with the least toxic and most effective drugs for their tumor. New approaches are needed to improve the care of cancer patients through new drug development, rational treatment planning, and reduced toxicities. The goal of this proposal is to address these gaps in drug development and treatment planning in PDAC, by directly measuring how different subtypes of cells within the same tumor respond to drugs. By extracting patient tumor samples and growing them in specialized conditions, tumor organoids (tumors in a dish) from individual cancer patients will be grown in the laboratory. Using a new imaging technology, individual cells will be assessed for drug responses while they are still growing side-by-side in a tumor organoid, mimicking what happens in a real tumor. The tumor organoid drug response data will be compared to real tumors taken from patients undergoing drug treatment before surgery so that this single-cell assessment technique can be validated as a way to measure heterogeneous drug responses in human PDAC. This novel approach to examine drug effects in heterogeneous tumors holds great promise for rational, personalized drug development and treatment planning.

Updated: May 2016