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Creating functional organoids from a patient’s tumor tissue allows researchers to test different treatment options in a realistic environment to predict what’s most likely to benefit that patient.
A key aspect of this research is observing treatment impacts and cell growth over time without altering the sample, which is where the photonics-based imaging approaches developed in Dr. Melissa Skala’s lab shine.
“What my lab contributes is imaging technology that can measure the way those cells produce energy to divide and grow, and then use that as a measure of their response to the drug treatment,” said Skala, who is a professor of biomedical engineering and medical physics at UW, a member of the UW Carbone Cancer Center, and the Carol Skornicka Chair at the Morgridge Institute for Research.
Skala and her team develop optical imaging technologies that use light to take advantage of a naturally-occurring glow of molecules within cells. By measuring how much light is given off and how quickly, her team can quantify how effective a treatment is without altering the tumor organoid. This allows continuous use of that organoid to evaluate treatments.
“Normally if you want to measure a drug response, you have to kill your sample and then assess it,” Skala said. “That is not an option here. We need to watch how things evolve over time.”
Skala collaborates on this research with Dr. Dustin Deming, who serves as co-director of the Precision Medicine Molecular Tumor Board. This statewide consortium of cancer clinicians and researchers serve as a free resource to analyze tumor genotypes and molecular abnormalities from a patient’s tumor sample to recommend targeted therapy options as well as ongoing clinical trials. Deming creates tumor organoids based on patient samples submitted to the board.
Skala and Deming are expanding their work to also study methods of combining and staggering multiple drugs to optimize treatment. While a drug may work very well initially, it can lose its potency over time as the cancer becomes more resistant.
“The questions are which drugs do we choose to pair? How much of each drug do we give? How long do we give it before switching to the next drug? Those are questions we can easily test in these organoid cultures and create a treatment plan that makes sense for the patient, so we can maximize their response to great drugs that they would otherwise develop a resistance to,” she said.
Skala’s imaging techniques also are useful in optimizing immunotherapy treatments. She is working with pediatric oncologist Dr. Christian Capitini and Dr. Krishanu Saha, associate professor of biomedical engineering at UW, to study methods of enhancing CAR T-cell growth conditions to create cells with the greatest potency to attack cancer cells when re-injected into the patient.
Like with the tumor organoids, Skala’s imaging techniques offer a non-invasive method of studying the metabolic activities of the cells.
“We’re trying to identify exactly how we could optimize artificial growth conditions for cells to give them the best chance of performing when they go back into the body,” she said. “And it turns out that energy, how much those cells are eating and how they use that fuel to grow and produce molecules, is a key feature of how well they will do when they get back into the body and how well they will fight the cancer.”
Skala enjoys partnering with cancer researchers to curate the best treatment options for patients.
“I’ve always been interested in personalized treatment planning because I think it’s important if we have the right tools, the right drugs to help people, we should use them in the wisest way possible so that people benefit,” she said.