The takeaway:
CU Anschutz is building a precision medicine platform that uses patient-derived tumor organoids to help identify personalized treatments for rare cancers. Led by Alice Soragni, PhD, the initiative aims to move organoid testing from the research laboratory into a validated clinical assay, meaning physicians can use the information to make decisions about patient care and guide treatment decisions.
Research for the sake of research is a concept that doesn’t sit well with Alice Soragni, PhD. If the knowledge she gains in the lab isn’t helping people, she chooses to find new paths ahead.
It’s why the renowned researcher chose to relocate her lab to the University of Colorado Anschutz. Because according to Soragni, CU Anschutz has what it takes to take science that “last mile” – reaching patients with rare cancers and the doctors who treat them.
Soragni is a professor of Biomedical Informatics and Neurosurgery and the Marsico Chair in Excellence in Functional Precision Medicine. She also serves as director of the Functional Precision Medicine Initiative in the Colorado Center for Personalized Medicine (CCPM).
As her lab continues developing models of rare cancer tumors, she’s excited for the less glamorous part of this work: getting the discoveries from her lab to the patient’s bedside. Her goal is to integrate the organoid platform into existing clinical laboratory infrastructure so patient tumors can be used to generate functional drug response data that physicians can use to inform treatment decisions at scale.
It’s a capability still rare in clinical care but possible, thanks to CU Anschutz’s leadership and infrastructure.
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Soragni describes her work in the lab as the “wild west” of ultra-rare cancers. No standard of care exists in the clinic for many of these cancers. Some tumors and tumor types can successfully be studied in the lab by using cancer cells to create “cell lines,” or implanting tumor tissues into animal models. But not all can be recreated in the lab. Rare tumors make these processes even harder.
“You simply don’t have the numbers,” Soragni said.
Soragni’s lab creates organoids – miniature “tumor avatars” grown from a patient’s own tumor cells taken during surgery or biopsy. The work in her lab focuses in particular on short-term models that preserve the tumor cells and include the surrounding cells, which are important as these cells influence how tumors grow and respond to drugs. This makes organoids more clinically relevant than traditional cell lines that isolate only the cancer cells.
Soragni's laboratory recently pioneered an organoid platform, described in Nature Protocols. Using label-free imaging and artificial intelligence (AI), the platform continuously tracks how individual organoids respond to drugs, revealing differences within tumors conventional methods can miss.
“This platform is really powerful because it allows you to monitor individual organoids in an unbiased manner. You can capture thousands and thousands of organoids in each condition and potentially identify those rare treatment-resistant tumor cells,” Soragni said.
The platform gives researchers the ability to scale, screening more conditions in a more robust way. Previous studies have shown that testing certain drugs for rare cancers often leads to finding what does not work for treatment. The more drugs you can test at once, the better. In previous studies, Soragni has seen the need to screen hundreds of drugs and combinations to find something that’s promising for a specific patient.
It’s the treatment for the individual patient that matters most to Soragni, and why she thinks this functional precision medicine approach is so powerful.
“It allows us to study that one rare tumor right there and then and potentially find something that works – something we would otherwise have absolutely no clue about because there simply isn't enough data.”
Understanding rare cancers is important to the patients who receive these diagnoses. But the information gleaned from platforms such as this is also important for understanding recurrence and treatment resistance for all cancers.
“Platforms like this allow us to gather high-resolution information on how a tumor responds to treatment, follow the cells and see what happens to them,” Soragni said.
Definitions:
Biomedical informatics: The science of using data, computing and artificial intelligence (AI) to improve research, healthcare and patient outcomes.
Cell lines: Cancer cells that are grown and maintained in the laboratory so researchers can study how tumors behave and test potential treatments.
Organoids: Miniature, three-dimensional models of a patient's tumor grown from their own cells that closely mimic how the tumor behaves in the body.
Label-free imaging: A technique that allows scientists to observe living cells and tissues without adding dyes or fluorescent markers that could alter their behavior.
Functional precision medicine: An approach to personalized medicine that tests how an individual patient's living tumor responds to different drugs to help identify the treatment most likely to work.
The research platform described in Nature Protocols is exciting for Soragni. But even more exciting to her is the work being done behind the scenes at CU Anschutz.
The lab has generated a lot of evidence showing these organoid models mimic patient responses, Soragni said, making them clinically relevant. But that leads to her bigger question: How do we get this data to the patient?
“That is what I was brought here to do. We are continuing to push the science forward, but the additional focus here is implementation: building the infrastructure required to move functional precision medicine into clinical care, so physicians can use these data alongside molecular and clinical information to inform treatment decisions for patients with hard-to-treat tumors,” she said.
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Currently, Soragni is building out a functional precision medicine initiative with CCPM. While her laboratory continues to develop a broader portfolio of organoid technologies, including the advanced imaging platform described above, the clinical effort is beginning with a streamlined version of her one-week-turnaround mini-ring organoid assay.
Together, they are validating the organoid assay for implementation within CCPM’s CLIA-certified, CAP-accredited clinical laboratory. Once the process is complete, results from the assay can be reported clinically – meaning physicians can use the findings as clinical information to help support treatment decisions – rather than the results being limited to research use.
It’s a resource-intensive process. Soragni is grateful for CCPM’s resources and existing infrastructure.
“We’re not reinventing the wheel,” she said. “We’re plugging our system into an existing CLIA/CAP laboratory that already operates at scale, which allows us to move at the speed of light.”
The data derived from the organoid screening platform combined with DNA and RNA sequencing, molecular characterization and other analyses will, over time, help to identify new biomarkers for drug responses. This, Soragni believes, can lead to simpler tests and better medicines.
Her hope is to help as many patients as possible.
“Whether it’s someone with a newly diagnosed rare tumor or someone with recurrent disease, my hope is that 10 years from now, technologies like this will simply be accessible."
Key points:
CU Anschutz is conducting research and building clinical infrastructure to improve treatment for patients with rare cancers.
Alice Soragni's laboratory creates patient-derived organoids that closely model how individual tumors respond to therapy.
AI-powered high throughput organoid screening can evaluate hundreds of potential treatments for patients with hard-to-treat, rare and ultra-rare cancers.
The Colorado Center for Personalized Medicine is working to translate this research platform into a validated clinical assay, meaning physicians can use the information to make decisions about patient care.
The long-term goal is to make functional precision medicine part of routine cancer care.