Six to eight children in the Netherlands are diagnosed with a malignant liver tumor each year. They are treated with chemotherapy and surgery. The treatment often involves a liver transplant, an invasive surgery meaning children need to be on drugs that suppress their immune system for their entire lives. ‘Most children with a liver tumor tend to have a good outcome from their treatment with chemo and an operation,’ says dr. József Zsiros, childhood oncologist at the Princess Máxima Center specializing in liver tumors and global expert in the field. ‘For children with a high-risk liver tumor, we have seen improved outcomes thanks to new chemotherapy approaches in the latest SIOPEL-4 treatment protocol, but survival is far from optimal. We expect that we can make big advances by putting the knowledge gained in lab research into clinical practice.’
Targets for therapy
Dr. Weng Chuan Peng, who leads a research group at the Máxima looking at childhood liver cancer, agrees. ‘In my group, we work with preclinical data from 3D mini liver tumors in the lab, known as organoids. This allows us to do large scale drug screens, identifying possible targets for therapy by looking at the effect of different drugs on the organoids. Together with József and other colleagues, within the Máxima and internationally, we can then test the benefit of drugs hitting the most promising targets within a clinical trial.’
Zsiros has led the most recent three international clinical trials for children with liver tumors that have shaped the current treatment. With SIOPEL, the global network and European collaborative study group of clinicians and scientists working on childhood liver tumors coming together this week, discussing the next SIOPEL-Explorer trial is an important aim of the SIOPEL Annual Meeting. Zsiros: ‘We plan to add a targeted treatment to the existing chemotherapy treatment, with the aim of improving response and survival for children with a high-risk liver tumor. We expect this European clinical trial to open soon. This trial is the first step, and we can build on that integration of pre-clinical discoveries from there.’
Growing community
‘The small number of children with a liver tumor is part of the reason that the integration of fundamental and clinical research has lagged behind compared to other forms of childhood cancer,’ says Zsiros. ‘The international research community focusing on liver tumors is also small, but growing. It’s exciting to see new people and personalities coming along and to see how we can integrate their new ideas and approaches into the historical research lines. I’m especially happy to see the integration of fundamental research into the clinic – and also the other way around. In the clinic, we see the gaps in our knowledge that we can take to our pre-clinical colleagues to help generate new research questions. That interaction is one of the key aspects of the SIOPEL Annual Meeting that I’m looking forward to.’
Peng adds: ‘The SIOPEL meeting at the Máxima is a great opportunity to meet the leading scientists and clinicians in childhood liver tumor research, and to see how we can translate our preclinical findings into clinical benefits for children. It’s also exciting to see so many disciplines coming together. We’re bringing together experts in immunotherapy, nuclear medicine, single cell genomics, theranostics, and many more fields. Liver tumors are very rare, so it’s important to foster such collaboration with diverse expertise to see how we can contribute to better outcomes for children.’
Close partnership
To conclude, Zsiros and Peng highlight the significance of a close partnership between the lab and clinical practice, made possible by the integration of childhood cancer care and research when the Máxima opened its doors five years ago. Zsiros: ‘Fundamental research on childhood liver tumors did not exist in the Netherlands before Peng joined the Máxima. Without a partner like him you’re in a sense one-handed, only covering the clinical side of the problem. Similarly, to do lab research without the tissue samples and expertise from the clinic would be much slower.’
Peng: ‘As a research hospital, the Máxima has offered us the perfect framework to integrate these two sides of the coin: we meet regularly, including at the M4C (Máxima Comprehensive Childhood Cancer Center) meetings. Our partnership has enhanced our way of thinking, strengthened our work on clinical trials and boosted our grant applications. With that, the research hospital setting accelerates both pre-clinical and clinical research, and makes us an important player on the international stage.’