Neuroblastoma is a tumor of the nervous system that can occur throughout the body. Around 25 children in the Netherlands are diagnosed with the disease each year. Even after intensive treatment, the cancer often comes back. One reason is that standard methods—like examining bone marrow under a microscope—cannot always detect tiny amounts of remaining cancer cells. As a result, a child may seem cancer-free while tumor cells are still present. This makes it important to pick out those children with residual disease, so their treatment plan can be adjusted if necessary.
Detecting ‘hidden’ cancer cells
In the Tytgat group, Van Zogchel researched a new way to find these hidden cancer cells: the so-called ‘liquid biopsy,’ essentially a blood test. Instead of only looking at cells under a microscope, this test searches for small fragments of genetic material (DNA or RNA) from the tumor in blood or bone marrow. This approach is far more sensitive and less invasive for the child.
Her research had two parts. First, she studied children with neuroblastoma using a technique called RT-qPCR, which can measure tumor RNA in bone marrow with great precision. RNA acts as a messenger for DNA. This method proved better at predicting which children are likely to relapse compared to standard microscopic analysis.
In the second part, Van Zogchel focused on tiny fragments of tumor DNA in the blood, known as circulating tumor DNA (ctDNA). Using advanced techniques such as digital PCR (a method to detect very small amounts of DNA) and sequencing (reading the DNA code), she showed that these fragments are a strong indicator of disease progression. These tests also look promising for other childhood cancers. They allow doctors to see earlier whether treatment is working or if the cancer is coming back. This enables doctors to tailor the treatment plan to each individual child.
Better predictions
‘These new biomarkers give us a measurable signal in the blood that shows whether cancer is still present,’ says Van Zogchel. ‘That means we can better predict which children might relapse and act faster if needed.’
‘With these new blood and bone marrow tests, we can monitor much more accurately whether the cancer is truly gone. That offers hope for quicker and more effective treatment if the disease comes back.’ She is proud that her work is already being applied in a clinical trial setting, both at the Máxima and Europe-wide: ‘It’s great to see that our tests are really used in clinical practice.’
Dr. Lieke van Zogchel defended her PhD thesis on October 14. Her research was supported by KWF Dutch Cancer Society, Maarten van der Weijden Foundation, Stichting aMEESing Mees, Stichting 100% Judith, and Stichting Koppie-Au.