In recent articles, we highlighted Inducable Pluripotent Stem Cells (iPSCs) and Cancer Stem Cells as breakthrough approaches in cancer treatment and diagnosis. Today, we’re “leveling up” with these techniques through our “3D glasses”: organoids.
The landscape of cancer research is constantly evolving, with innovative approaches revealing new insights into the disease at cellular and molecular levels. Among these advances, organoids—miniature, three-dimensional tissue cultures—have opened promising avenues for studying cancer biology and developing more effective treatments.
I had the opportunity to discuss the role of organoids in cancer research with Dr. Lena Wedeken, the head of the laboratory at CellPhenomics, a biotech company based in Berlin, Germany. Their focus is on establishing and cultivating complex patient-derived cell culture models (PD3D®) and organoids from various solid tumors for research and personalized toxicity testing.
Organoids are 3D structures that replicate the complexity of human organs, including their architecture and function. This innovation is monumental for cancer research. Organoids are derived from iPSCs or tissues that more accurately mimic the architecture and function of specific organs. While organoids incorporate previously discussed 2D cell culture techniques, they offer more. By closely resembling real human tissues, organoids provide a more realistic model for studying cancer growth, invasion, and treatment responses.
Organoids: 3D Glasses of Cancer Research
A recent study published in Scientific Reports in April 2024 caught my attention for its innovative approach to pancreatic cancer, one of the most challenging cancer types. Pancreatic cancer is notoriously resistant to immune therapies due to its highly immunosuppressive behavior. Given the poor prognosis associated with pancreatic cancer, where survival rates remain low, this research offers a glimmer of hope. The researchers developed a 3D platform using pancreatic cancer organoids, enabling the monitoring of interactions between cancer cells and T cells.
The key finding was that different organoids exhibited varied responses to T cell-mediated killing, revealing specific vulnerabilities in some tumors. This insight could lead to tailoring immunotherapies for individual patients, potentially enhancing treatment outcomes for pancreatic cancer.
Through this approach, researchers identified specific signaling pathways that tumors use to avoid immune responses, explaining why current treatment strategies have struggled to be effective in pancreatic cancer. These findings are exciting, as pave the way for new therapeutic targets. By blocking these immunosuppressive pathways of tumors, we may improve the efficacy of immunotherapy for pancreatic cancer patients, as well as other cancer patients. After reading this research, I felt compelled to talk about the role of organoids in the cancer field. So, what do organoids bring to the cancer field?
In a conversation for Breaking Cancer News, Dr. Wedeken encapsulated the role of organoids in cancer research.
“Organoids derived from cancer are a powerful tool for research and drug development and are gaining increasing impact for personalized medicine,” she said. “They robustly recapitulate the characteristics of the original cancer, developing as a self-organized 3D structure while expressing key markers and retaining the genetic profile of the original tumor. Each organoid model represents its parental tumor, displaying phenotypes of resistance and sensitivity to various drug treatments and radiation. They can be genetically modified, expanded, and are compatible with high-throughput systems, offering the whole toolbox of an in vitro model. Plus, they can be established, and drug tests can be performed within a therapy-relevant timeframe for the patient from whom they were derived.”
Organoids Can Increase the Efficacy of Cancer Treatments
When I asked Dr. Wedeken about the main influence of organoids in the cancer field, she emphasized their utility in treatment decisions.
“Organoids can be used in personalized medicine: a sample from a patient tumor is taken, organoids derived and validated, and then drug treatments are performed on the organoids to determine which drugs are effective,” she explains.
This information can then be combined with genetic data from tumors to guide treatment decisions for the patient. “Several studies have already shown an extremely good negative prediction rate of organoids for clinical response and a very good positive prediction,” she adds.
“Furthermore, cohorts of organoids, each representing a different patient, can be used to screen existing drugs, new combinations, or new drugs. The results can be integrated with genetic data to identify or validate biomarkers of treatment sensitivity, which can significantly influence cancer treatment strategies,” said Dr. Wedeken.
The Path Forward
Dr. Wedeken also addressed the limitations of organoids.
“They have the typical limitations of in vitro models, such as not representing a whole organism or metabolism,” she said. “Some of these challenges can be addressed by using co-culture systems or integrating organoids into microfluidic/on-chip systems. Additionally, other in vivo models can complement organoid studies. For example, organoids can be used for initial screenings and then verified in different models.”
Finally, Dr. Wedeken expressed optimism about the future of organoids.
“They are gaining increasing interest in research, particularly for more complex co-culture models and their integration with on-chip technologies. Organoids are becoming an important factor in achieving the 3D concept in preclinical drug development, complementing and supplementing other in vitro and in vivo models. They are also being used in ongoing and planned clinical trials to assess their value in guiding treatment decisions. This will support the widespread acceptance of organoids in personalized and functional precision oncology, as well as other disease fields.”
