Pancreatic cancer is considered one of the most difficult forms of cancer to treat. A key reason for this is that tumors do not exist in isolation but are embedded in a complex environment of blood vessels, connective tissue, and immune cells. It is precisely these interactions that determine how the disease develops and responds to therapies.
Researchers at UTHealth Houston have now taken a significant step toward better understanding these dynamics. Led by Faraz Bishehsari, they developed a so-called 'tumor-on-a-chip': an advanced model system that mimics the tumor environment outside the body. The results of the study have been published in Advanced Science.
From patient to chip
For the model, the researchers used tumor and blood samples from patients. From these, three-dimensional organoids were cultured. These are so-called miniature versions of tumors that retain key characteristics of the original cancer.
These organoids were then placed in a microfluidic chip, along with blood vessel cells, stromal cells, and immune cells. This setup creates an environment that closely resembles that of the human body. The chip uses fluid flows that mimic blood circulation, allowing researchers to track how cancer cells behave and respond to treatments.
According to Bishehsari, this is a significant improvement over traditional laboratory models. “We wanted to develop a system that realistically represents not only the tumor itself but also its interaction with the environment,” the researcher said.
Scar tissue and treatment resistance
One of the study’s key findings is the role of so-called desmoplastic stroma, a dense, scar-like tissue that surrounds the tumor. This stroma often acts as a barrier to drugs and plays a crucial role in treatment resistance.
Using the tumor-on-a-chip model, researchers were able to closely observe the interaction between cancer cells and the tissue. It became clear that the stroma not only protects the tumor but also actively contributes to its growth and resistance to treatments.
Interestingly, it turned out that specifically targeting these stromal components can improve the effectiveness of chemotherapy. This points to new treatment strategies that address not only the tumor but also the surrounding tissue structure.
Studying immune responses
In addition to stromal interactions, the model also offers opportunities to study immune responses. This is of great importance because the immune system plays a key role in the response to cancer therapies, such as immunotherapy. Traditional models often fall short here because they cannot adequately simulate these complex interactions.
By utilizing advanced imaging, molecular analysis, and drug testing, the researchers were able to demonstrate that the chip model accurately reflects the behavior of real tumors. This makes the system suitable for testing new therapies and predicting treatment outcomes.
Personalized treatment
The tumor-on-a-chip model fits within a broader trend in cancer research, where there is an increasing focus on patient-specific models. Combining organoids with microtechnology creates a powerful platform that bridges the gap between laboratory research and clinical practice.
The researchers aim to further develop the technology, with a focus on scalability and broader applicability. Ultimately, the system should contribute to the faster and more effective development of new drugs.
Tumor-on-a-chip platform
Last year, an innovative 'tumor-on-a-chip' platform was developed that provides insight into how tumors fend off immune attacks. This system mimics a living, vascularized lung tumor and allows for real-time observation of how CAR-T cells attempt to attack cancer cells.
Researchers then demonstrated that endothelial cells temporarily emit signals that guide immune cells to the tumor. When these signals disappear, the cells lose their direction. By administering the diabetes drug vildagliptin, these signals are maintained, allowing more immune cells to reach the tumor.
