The grant of 150,000 euros is intended as follow-up funding for earlier research that was financed by KWF. With the grant, the researchers gain access to techniques and models that are closer to the patient, allowing them to further develop their results towards initial clinical studies.
Selection of the most promising tumors for treatment via sugar inhibition
Cancer cells have developed clever ways to escape the immune system. One way is the use of special sugar molecules, sialic acids, which are present in large quantities on the cancer cell surface. These sugars bind to Siglecs, proteins on immune cells that normally provide inhibitory signals. The result is that immune cells become less active and cancer cells can grow and metastasize undisturbed. Our research team is developing a new drug that blocks this process. The drug prevents cancer cells from incorporating sialic acids. In laboratory tests and animal models, we saw that our drug strongly inhibits tumor growth and metastases, without serious side effects. This makes the drug a promising candidate for a new cancer therapy.
An important question, however, is for which cancer types this drug will be most effective. Until now, we have mainly relied on mouse models and gene expression data from tumors. This provides valuable insights, but does not always predict how many sialic acids are actually present on the cancer cell. Moreover, mice and humans differ in their sialic acids and Siglec proteins, which means that results from mice are not always easily translatable. With this KWF BOOST project, we want to solve this problem by examining human tumor tissue on a large scale and directly for the first time. The research will produce a ranking of cancer types and disease stages in which sialic acids are most present. These are the tumors where our drug will be most promising, either alone or in combination with other therapies.
Through this research, we will obtain a reliable picture of which cancer types and disease stages are most dependent on sialic acids to suppress the immune system. This will allow us to determine much more specifically for which patients our drug can best be used. This prevents clinical trials from being conducted with the wrong patient groups and accelerates the path to successful application. The results will be directly incorporated into our existing development strategy for sugar inhibitors. In this way, we are making the step from laboratory to clinic smaller and increasing the chance that our drug will develop into a new, effective treatment against cancer.
ORGATRIX-in-actie: geneesmiddel- en therapietesten met hoofdhalskanker
Paul Kouwer & Marleen Ansems (Radboudumc)
For developing better treatments against cancer, good laboratory models are needed. Such models should show how a tumor develops, and also predict how the patient responds to treatments. Animal models provide only a limited picture of human cancers. Better models are based on tumor organoids: cultured mini-tumors from patient cells. While they mimic many properties of real tumors, there is a problem: they grow almost exclusively in animal-based materials, such as Matrigel or Cultrex, that are protein mixtures derived from mouse tumors. These materials are poorly defined, variable and non-adaptable, which makes research into factors that influence tumor growth and treatment difficult. Moreover, the use of animal material is unethical and undesirable.
In the ongoing ORGATRIX project (2024–2026), we are developing a fully synthetic gel, the PIC hydrogel, in which we grow head and neck cancer organoids. This gel is well-defined, reproducible and modifiable. This allows us to mimic tumor properties, such as tissue stiffness, much more reliably. Stiffness is an important factor that partly determines how aggressive a tumor is and how it responds to treatment. Our initial results are promising: head and neck cancer organoids grow excellently in the PIC hydrogels.
With ORGATRIX-in-action, we are taking the step from making reliable head and neck cancer organoids to their application in drug and therapy testing. ORGATRIX-in-action should deliver a functional and clinically relevant screening platform in which the effects of patient-specific tumor characteristics on therapy response can be systematically investigated. The result is a reliable, reproducible and animal-free model that significantly increases the predictive value of organoid-based tests.