Antonio Pérez-Martínez (second from the left, at the back), at CNIO with his group from the Paediatric Haematology and Oncology Clinical Research Unit IdiPAZ-CNIO. Credit: Pilar Gil / CNIO.
Paediatric cancer is the leading cause of death among children and teenagers in developed countries. It is a different disease from cancer in adults, and much less is known about it.
“It’s time to create personalised strategies for children and teenagers, too, to offer them more effective options with fewer side effects,” says Antonio Pérez-Martínez, director of the new IdiPAZ-CNIO paediatric cancer unit.
“We urgently need to investigate: we need shorter times, so that the results reach the patients sooner,” says Pérez-Martínez.
They will look for alternative therapies for ‘forgotten’ tumours, advances in immunotherapies already established in adults, new mechanisms to attack brain tumours and the creation of organoids and ‘labs-on-a-chip’ to test drugs.
In children, cancer is a rare disease, which is cured – with treatment – in eight out of ten cases. But it is also the leading cause of death in children and teenagers in developed countries, and its therapies have not improved at the same rate as for adult cancers. The National Cancer Research Centre (CNIO) now has a new IdiPAZ-CNIO Mixed Unit for Paediatric Haematology and Oncology Clinical Research, led by paediatric oncologist Antonio Pérez-Martínez, which seeks to change this situation.
Targeted and personalised therapies, which directly target the genetic alterations of each individual patient that cause the disease, are improving cancer treatment in adults. However, in children and teenagers, traditional, aggressive and highly toxic cancer treatments are still generally used.
This is due to a lack of understanding about paediatric cancer. In fact, it is a different disease to cancer in adults and is less studied; in the absence of a better understanding of its causes on a molecular scale, its treatments are still not specific to the disease of the patient in question.
“It’s time to try to incorporate more targeted and personalised strategies”
“We know very little about how cancer appears in children. In developed nations, we manage to cure most of them, but with highly intense treatments”, says Pérez-Martínez, who is head of the Paediatric Haematology and Oncology service at the Hospital Universitario La Paz (Madrid) and director of the CRIS Advanced Therapies Unit at the Hospital Universitario de La Paz.
“It’s time to try to incorporate more targeted and personalised strategies, traditionally developed in adults, to offer fewer adverse effects in children. To do this, I believe that collaboration with CNIO is essential,” adds Pérez-Martínez, whose research is funded by the CRIS Cancer Foundation.
“So results reach the patients as soon as possible”
Childhood cancers account for 0.5% of new cancers, and they are very different from those in adulthood. They present more acute and aggressive symptoms, and are located in the blood, lymphatic system, or supporting tissues – not in the breast, lung, or prostate. They even appear in different areas of the brain. In addition, tumour cells accumulate fewer mutations in children than in adults, and the immune system response, for example, is different.
Pérez-Martínez once again highlights the “urgency” of the situation: “We need shorter times for results to reach patients, that’s another goal of our unit,” he says. They aspire to achieve this by combining the technological equipment of CNIO and the experience of its staff with the reality of clinical cases: “Direct contact with patients and their families can drive us to transform the knowledge generated from this type of basic-clinical consortia into patents as soon as possible.”
New CAR-T cell therapies
CNIO’s ability to perform genomic analyses on large quantities of samples may be applied, for example, to the search for new drugs for patients who do not respond to available treatments.
Personalised treatments that use the immune system to attack tumour cells will also be investigated, such as CAR-T therapies – in which the patient’s T lymphocytes are given the ability to fight the tumour. Researchers will also study how to monitor the response to treatments through simple blood tests, known as liquid biopsy.
The shortage of samples and patients for clinical trials, an obstacle derived from the low incidence of paediatric cancer, will be addressed by improving the experimental models on which to test treatments.
Alternatives to the lack of samples
Specifically, the new unit will investigate organoids – cell cultures that grow in three dimensions, thus better simulating the structure of tissues in the body – and ‘lab-on-a-chip’ devices that perform miniature laboratory analysis.
For specific tumours, research will focus on detecting haematological tumours – of the blood or lymphatic system – sooner and better. One of them is juvenile myelomonocytic leukaemia, a “forgotten” disease whose only effective treatment today is transplant – achievable in only 50% of cases.
Sarcomas and brain tumours
In more malignant brain tumours, the main difficulty is getting the treatments to reach them. The team will look for new drug infiltration pathways and direct them to the non-tumour cells that influence the tumour – the tumour microenvironment. With regard to another type of tumour in the nerve tissue, neuroblastoma, they will try to neutralise it by influencing the way its cells metabolise iron.
To prevent metastasis in sarcomas (bone or soft tissue tumours), research into cell therapies with antibodies will continue.
“We currently have a clinical trial with one child, whose treatment includes cells from his identical twin brother. It is based on a discovery made in a previous project by IdiPAZ and CNIO. It is an example of the benefits of collaboration between those who are in contact with patients and basic research,” explains Pérez-Martínez. “But seven years have passed. We need shorter times. It’s urgent.”
The current projects being carried out by this new unit are funded by the Cris Cancer Foundation through an agreement with CNIO.