With a liquid biopsy, the pediatric oncologist can obtain information about the tumor by examining a small sample of blood or cerebrospinal fluid. These fluids contain fragments of DNA or other molecules from cancer cells, which provide important information about the cancer and are also known as 'biomarkers.'
Value for children with cancer
‘Liquid biopsies can be valuable at any point in a child’s cancer journey,’ says Leendert Looijenga, Professor of Translational Germ Cell Oncology and Fertility at the University Medical Center Utrecht and research group leader at the Princess Máxima Center. ‘At the Máxima, we already analyze many cancer characteristics to determine the diagnosis. Liquid biopsies help confirm the diagnosis and determine the aggressiveness of the disease. They aid in monitoring the response to treatment and allow for treatment adjustments. Liquid biopsies enable us to see how the child responds to treatment.’
When a pediatric oncologist needs information about cancer, it often comes from a tissue sample taken from the tumor, known as a ‘tissue biopsy’. Obtaining a tissue sample can be challenging, for example, if it is small or located in a difficult place, and can also cause complications.
Looijenga states: ‘Drawing a small amount of blood is much easier. For optimal treatment, you want to ensure no cancer cells are present. Other techniques, such as scans, do not always provide that certainty. Liquid biopsies can provide a better picture of the tumor and any metastases.’
Biomarkers in germ cell tumors
Looijenga conducts significant research into germ cell tumors, which are tumors arising from precursor cells that normally develop into eggs or sperm cells. It is one of the most common types of cancer in young men. ‘For germ cell tumors, we have identified good biomarkers now used for tissue analysis, transforming clinical practice. Unfortunately, these biomarkers are not suitable for liquid biopsies. Therefore, we are currently investigating micro-RNA.’
RNA is a molecule that translates information from DNA to the cell, and micro-RNA assists in this process. Germ cell tumors produce a large amount of micro-RNA, which is released into the blood and cerebrospinal fluid. ‘With a special technique, we can measure the micro-RNA in children with a germ cell tumor,’ Looijenga explains. ‘This provides information about the cancer cells. In an international study, we investigate whether studying micro-RNA can provide additional information to determine the appropriate treatment for a child. I expect that in the future, we will be able to determine whether a child with a germ cell tumor will benefit from chemotherapy and how intensive the treatment should be.’
Overview of liquid biopsies
Together with many colleagues from the Máxima, Looijenga recently published a review article in npj Precision Oncology on liquid biopsies in children with solid tumors. A solid tumor is cancer that arises in a solid organ, such as the liver or kidneys. The first author is Ferd Janssen, a PhD candidate in Looijenga’s research group. He explains, ‘We have compiled the knowledge about liquid biopsies for a large number of solid tumors. We have provided an overview of potential biomarkers for neuroblastoma, germ cell tumors, and tumors in the liver, kidneys, bones, and muscles.’ Looijenga adds, ‘This article serves as a foundational work upon which we can build to optimize current possibilities.’
The Máxima participates in various international studies on liquid biopsies in children with cancer. One of these studies is the MONALISA study, an EU project investigating the clinical application of liquid biopsies in children with relapsed neuroblastoma. Professor Lieve Tytgat is the international co-principal investigator, and the Princess Máxima Center sponsors this study.
Towards clinical practice
‘Of course, we want to implement these possibilities in clinical practice as soon as possible,’ Looijenga says. ‘To do this, we need to determine which techniques and biomarkers are most suitable for each type of cancer. We can make these steps much more effectively now, allowing us to anticipate the faster use of biomarkers in the clinic. However, we must first thoroughly validate these promising biomarkers to confirm that their potential is real and not coincidental. Additionally, clinical studies are necessary to demonstrate the added value of liquid biopsies compared to current methods. We must also find biomarkers for cancers that currently lack good ones.’
He continues: ‘It is important to design these studies so that the techniques can be rapidly implemented in clinical practice. You can develop amazing techniques, but if they are too complex or expensive to apply, they are of little use. Therefore, we must strive for feasible and cost-effective methods to truly improve care for children with cancer, both in the Netherlands and in other countries.’
International collaboration
Looijenga emphasizes the need for international collaboration: ‘Collaborating with other pediatric cancer centers and conducting analyses together is crucial. This ensures a structured approach and better comparable results. Biobanks play a significant role in this. They are databases where all samples are collected. Therefore, it is important that liquid biopsies are now a standard part of the Máxima’s biobank, made possible through financial support from KiKa. A well-established and maintained biobank fosters international collaboration and helps us make significant progress more quickly.’ The authors of the review article are researchers or doctors from the Máxima and international participants in liquid biopsy studies, including those on neuroblastoma, kidney tumors, rhabdomyosarcoma, other sarcomas, germ cell tumors, and brain tumors.
A standardized approach also aids in comparing results between different institutions. ‘By collaborating, we ensure that the best methods and techniques become widely available,’ Looijenga says. ‘In this way, each institution can benefit from the knowledge and experience of others. Together, we can elevate the care for children with cancer worldwide.’