Organoids to improve treatment outcomes for pancreatic cancer

At the Technical University of Munich (TUM), three-dimensional miniature tumors (organoids) with the structures and properties of pancreatic cancer have been grown in the laboratory for the first time. Prof. Maximilian Reichert, Head of the Center for Translational Pancreatic Cancer Research and Head of the Interdisciplinary Tumor Outpatient Clinic of the Gastrointestinal Tumor Center at TUM's Klinikum rechts der Isar, describes the new possibilities for clinical practice in an interview with MEDICA-tradefair.com.

What were the results of cultivating organoids from pancreatic cancer cells?

Prof. Maximilian Reichert: We use organoids in translational oncology to test which drugs effectively combat a tumor. Pancreatic cancer has a particularly high mortality rate. Only 30 percent of those treated respond to the very aggressive chemotherapy and even these become resistant to the therapy extremely quickly.

The challenge in pancreatic cancer is the intratumoral heterogeneity of the tumor cells, which contributes significantly to resistance to therapy. We wanted to further develop the organoid model and reduce this heterogeneity to make the target area for our therapies more focused.

How can this affect treatment?

Reichert: The tumor cell can adapt quickly to changing environmental conditions. Our hypothesis is that by reducing heterogeneity, the tumor cell is less able to do this, which we refer to as reduced plasticity. We hope that our approach will prevent this rapid development of resistance. This could make classic chemotherapies more effective.

This reduced plasticity and heterogeneity, resulting in a smaller attack surface, could be combined with completely new forms of therapy, for example immunotherapy or cellular therapy, and thus simply clear this population of tumor cells. This might even be possible without traditional chemotherapy with its severe side effects.

Is the procedure transferable to other tumors?

Reichert: We are trying to take our model entities, where we are developing these technologies, and then make them widely applicable to other tumor entities. Here at our institute, we apply the organoid system to all gastrointestinal tumor entities, from the esophagus to the intestine. Pancreatic cancer was a particular challenge for us because we see a particularly high degree of heterogeneity here and have therefore tested our concept here. We are currently investigating the application to bile duct carcinomas. This tumor entity is on the increase and will probably pose a similar problem to pancreatic cancer in the future.

What new challenges are posed by your research findings?

Reichert: Our task in translational research is to translate these research findings into clinical practice. To do this, we have to validate these findings using patient samples. The next step is an interventional study in which these concepts are applied to patients. This often involves combining an established procedure such as chemotherapy, which is used for pancreatic cancer, with a drug that can reduce this heterogeneity, for example.

Our research would not be possible without access to patient samples. In many cases, we cannot promise that the provision of cell material will have a direct impact on the patient's prognosis. We can only make progress in translational research by working together with the people being treated. That is why I am extremely grateful that so many people are willing to participate in the research projects.