When patients’ cancer cases prove resistant to standard therapies, oncologists must turn to innovative ways of uncovering treatments best suited for each individual.
One method for testing so-called precision cancer treatments involves taking a sample from a patient’s tumor and growing organoids—three-dimensional structures of cells that mimic organs—in the lab. It’s laborious, but allows researchers to test a range of drugs to identify fruitful treatment courses.
“They reflect the patient’s tumor a lot better than any other model that people have come up with,” says Daniel Gil, who recently completed his PhD in biomedical engineering at the University of Wisconsin-Madison.
But gauging the effectiveness of different treatments oftentimes involves breaking up the organoids or processing them in ways that render them useless for further examination. Other methods don’t yield robust information.
Along with Melissa Skala, a professor of biomedical engineering at UW-Madison, and Dustin Deming, an associate professor of oncology in the UW-Madison School of Medicine and Public Health, Gil recently demonstrated the effectiveness of a technique called wide-field, one-photon redox imaging as a means of measuring treatment response in patient-derived cancer organoids. They published their findings in a paper in the Journal of Biomedical Optics. An image from their study was featured on the cover of the journal’s March 2021 issue.
Redox imaging reveals the natural fluorescence of two common metabolic coenzymes, meaning it doesn’t require introducing external fluorescent dyes or molecules. Since most cancer treatments affect the metabolism of cancer cells, either directly or indirectly, redox imaging allows researchers to track metabolic changes as biomarkers of treatment response.
Gil says the imaging technique dates back to the 1960s, but advances in hardware and image processing have led labs such as Skala’s in the Morgridge Institute for Research on the UW-Madison campus to revisit it for studying cancer.
Because redox imaging doesn’t alter samples in any way, it can be used in parallel with other techniques. In the paper, Gil also demonstrated its effectiveness in tracking samples over time, which would allow researchers to use a single set of organoids to monitor ongoing treatment response rather than different batches for various points in time, as is typically the standard procedure.
“If you’re thinking about how to screen many drugs and drug combinations, the amount of patient material you have does become an issue,” says Gil, who started as a postdoctoral researcher at the University of Texas in spring 2021.
Redox imaging also requires dramatically less costly microscopes, compared to techniques that use multiphoton or fluorescence lifetime imaging microscopes.
“Before, our research was all with research-grade microscopes that were expensive and that no one had, so that’s the advantage of this approach: It’s actually accessible,” says Skala.
Skala’s group, in partnership with Deming, is already using redox imaging to evaluate treatment responses in colorectal cancer patient samples as part of clinical trials for therapies through the UW Carbone Cancer Center.
Author: Tom Ziemer