Jaume Mora Graupera is a pediatric oncologist and scientific director of the Oncology and Hematology Area at Sant Joan de Déu Hospital, where he also leads the developmental tumor laboratory. He is a physician member of the International Society of Pediatric Oncology and other national and international scientific societies. For his research work, he has received several international awards, and is the author of more than 75 peer-reviewed scientific articles in his specialty, which also includes six chapters of his in books published nationally and internationally.
Mora is one of the promoters and scientific director of the SJD Pediatric Cancer Center in Barcelona. This pioneering center has 37 individual rooms, 26 boxes for outpatient care, 8 chambers for hematopoietic progenitor transplantation, and 21 offices for external consultations. It has operating rooms, research laboratories, nuclear medicine service... It is 14,000 square meters designed to cure children and adolescents with cancer, a project carried out thanks to donations raised through the #ParaLosValientes campaign, which was fronted, among other people, by one of the founding donors of the center, footballer Leo Messi.
--- The starting point of this interview is a clarification: With the word cancer, we refer to the disease that affects adults and children, but the causes of cancer in both cases have nothing to do with each other. It is hard to understand, however, that, being so, the common designation has been maintained.
--- If we are here today ---at the SJD Pediatric Cancer Center Barcelona--- it is because of this question. The problem is that they bear the same name, people talk about cancer without further specifications, it is a conceptual error. More than ten years ago, at Sant Joan de Déu Hospital, we decided to create the Pediatric Cancer Center Barcelona (PCCB) because we realized that not even healthcare professionals understood the difference, because the specificities of childhood cancer were not clear. The consequences of this misunderstanding were many. One of them is that the great advances in adult cancer (breast cancer, for example) have not provided any real advance in pediatric cancers. We had to forge our own path.
--- What are the main differences that explain childhood cancer?
--- The main difference is that during the first quarter of our biological life we are growing. The growth stage ---in which we go from the fertilization of the egg to being a biological adult, a total of about 8,000 days according to the WHO (World Health Organization), that is, about 20-something years--- determines the diseases that affect us in this period. Because we grow, we have a type of diseases and also a specific type of tumors that, otherwise, we cannot suffer. This is the reason for developmental tumors.
--- Are they less common diseases than those of adults?
--- Diseases of aging are much more prevalent today given that the human population now lives significantly longer than ever before in human history. Diseases of aging (biological involution) are mainly cardiovascular, linked to lifestyle, obesity, and aging cancer. In contrast, in the first part of life, the first 25 years, things happen to us for the opposite reason. There is a transformation, a continuous change, a patient changes from year to year, and diseases of growth occur. The problem with cancer is that the same name is used for both children and adults, but the diseases referred to by this single word are, in adults, diseases of aging and, in children, diseases of development. Developmental tumors are all rare diseases, orphan diseases by definition.
--- All of them ---pediatric and adult---, however, involve abnormal cells.
--- In the case of adults, cells degenerate and accumulate mutations simply by repeatedly duplicating. Hence their incidence as we age. Everyone knows someone who has had breast, colon, or prostate cancer... With children, cancer has nothing to do with it, neither the type of lesions, nothing has to do with it. The name has led to confusion, because they are phenomena from opposite extremes. The fact of being in growth puts you at risk because some cells have a greater potential to grow in a disordered way, and therein lies the root of developmental tumors.
--- From what moment in life can these alterations occur?
--- The first alteration and necessary condition is a mutation in a cell during the fetal stage. In this period of life, we go from a fertilized cell to 6 trillion cells 9 months later. This is a brutal cell manufacturing process, a higher rate than that of any other tumor. However, our species is born biologically premature because, otherwise, the brain would not pass through the birth canal. We need a very long postnatal period, more than twenty years, to continue developing biologically. Thus, gestation is the process of most cell production that our body will experience throughout our lives. And it is the process of specifying the function of each cell that goes wrong in all developmental tumors.
--- What does that alteration, the cellular mutation, consist of?
--- By accident, a cell can mutate spontaneously, and that causes the cell to remain blocked in the undifferentiated state typical of the fetal period. It does not mature, it does not differentiate. Two-thirds of all spontaneous mutations in our entire lives occur during the growth period, especially during gestation. One only has to remember that 20% of all human gestations end in spontaneous abortion for this reason. Spontaneous mutations have nothing to do with exposure to external agents, elements of lifestyle, as happens in adult cancer. This is why developmental tumors have not changed their incidence with changes in lifestyle and are presented quite homogeneously in all regions of the world.
--- And once born, how does the risk evolve?
--- In the postnatal period, during the first two years of life, the breastfeeding period, up to 2-3 years, we have a very specific growth period determined by maternal nutrition (we are mammals) and very specific organs mature in this period. Only these organs will develop tumors characteristic of their maturation, such as the retina. Retinoblastoma, cancer of the developing retina, is a characteristic tumor of this period. Once the retina is formed, the risk of developing retinoblastoma is over, even if your cells are mutated by the retinoblastoma gene. Thus, one must have the mutation (necessary condition) and also have the organ in growth (sufficient condition). In this infant period, we also have other tumors such as hepatoblastoma (the tumor of the growing liver) or skin angiomas. 1% of all Caucasians have angiomas.
--- From infancy to puberty, many things also happen.
--- This period known as childhood or infancy, leads to confusion with "niño" or breastfeeding in English. It is a period characterized by slower and continuous growth, about 4-5 centimeters per year, a time of progressive brain development and maturation of the immune system (hence the high number of infections children suffer at these ages). Leukemia and gliomas are the characteristic tumors of this stage. For these tumors to appear, let's remember, one must have been born with the mutation (previous or necessary condition) and be in postnatal maturation of the organ in question (immune system or brain). The final period of growth is adolescence, when growth is 10 to 12 centimeters each year, for 2 years. It is a brutal growth, with an incredible calorie consumption. This accelerated development increases the risk of bone tumors and lymphomas. Each cancer occurs in a specific context, but the biological bases that explain childhood cancer is development. Each organ is at risk because there can be an alteration in the cell that generates that organ at the moment of its growth.
--- At what point is the cure for childhood cancer today?
--- More than 80% of all tumors we treat at the PCCB are cured. In North America (Canada and the US), more than 80% of childhood cancers are cured, the same as in Australia and Japan. In Western Europe (10% of political Europe, not including Poland), also, more than 80%. In Spain, the cure rate reaches 80%; in Latin America, it does not reach 50%; in Africa, not even 50% of childhood cancers are diagnosed. Therefore, the probability of being cured depends on where we live. Even so, for example, brainstem tumor, one of the brain gliomas that occurs in childhood, between 6-10 years, to this day, neither in Hamburg, nor in New York, nor here in Barcelona, still has no cure.
--- The SJD Pediatric Cancer Center Barcelona is a pioneer in Europe. But it was born in a hospital, Sant Joan de Déu, which was already excelling in the treatment of childhood cancer. What needed to be added?
--- Until we understood that childhood cancer research does not have to follow in the wake of adult cancer researchers, this center made no sense. Childhood cancer requires its own research and specific researchers. Researchers of aging cancer are very prominent, world-renowned oncologists, but they do not provide us with the necessary solutions for our patients. Specific research is needed, special dedication for these tumors.
--- What are your main research targets?
--- Each type of developmental tumor originates from each of the organs that must be generated for each new individual. Thus, each organ must be studied to understand each of the tumors that appear. For example, with researchers from the United States, we study neuroblastoma ---the disease that originates from the fetal precursors of the peripheral nervous system---. We also study sarcomas (Ewing's sarcoma and Osteosarcoma and Rhabdomyosarcoma), each type of leukemia, retinoblastoma, kidney tumor (Wilms' tumor), and more recently we have started with a very rare and aggressive type, rhabdoid tumors. And all our research is carried out with our own study model.
--- What is this unique research model like?
--- It is a research model called translational. Based on the patient we are treating with neuroblastoma, for example, we ask questions about their specific tumor. We look for the answers in the laboratory to apply in therapy, diagnosis, or prognosis. For each case, we generate a team of researchers that includes the expert in the clinical aspects of the disease from which the questions to be asked are derived. Together with basic researchers, a research plan is formulated that tries to resolve the issue. These research plans usually last between 5 and 7 years until we can return to the patient and test the answers. The final experiment is clinical trials. These clinical trials, with our patients, allow us to verify whether or not we have answered the question we asked ourselves at the beginning. This is the model, research from the patient to return to the patient. All these research programs are coordinated with families or patient associations that are involved in their design and funding.
--- What research do you have underway?
--- Our goal is to test in patients what we develop in the laboratory. As a result of this model, we have carried out 6 clinical trials, final experiments based on our own research. And we are especially proud of it. We have culminated laboratory findings in clinical trials in retinoblastoma, Ewing's sarcoma (x2), neuroblastoma (x2), and brainstem tumor (DIPG). We have the next ones ready in sarcomas, vascular tumors, rhabdomyosarcoma, and medulloblastoma, among others.
70% of our laboratory's budget comes from donations from families and associations, foundations that for 20 years have given us their unconditional and continuous support--- What is the balance of the program so far?
--- It has been so successful that we have been able to finance even this specific center for developmental cancer, the PCCB. Integrating families into the management and decision-making bodies has been key to getting us where we are.
--- We know the need and importance of research, but also the difficulties, often, in financing it.
--- 70% of our laboratory's budget comes from donations from families and associations, foundations that for 20 years have given us their unconditional and continuous support. The model has consolidated to the point that it is the families who drive us to continue growing. It was at one of the annual meetings we hold with our donors, in 2013, that one of the families asked me: Why don't you study my daughter's tumor? What do you need? ---they said---. And I immediately replied that what was needed to start a new line of research was 50,000 euros a year for three years. A month later, that family who asked about their daughter's case gave us a check for 150,000 euros. This is how, for example, we have a number of research lines that we never would have imagined.
--- For the construction of the PediatricCancerCenterBarcelona (PCCB), where has the greatest support for resources come from?
--- The PCCB has become a reality thanks to thousands of donations from civil society, highlighting the contribution of 15 founding donors ---footballer Leo Messi, among them--- who made the start of the works possible in 2018. In February 2017, the Hospital launched the #ParaLosValientes campaign with the aim of raising the necessary amount for the construction, with a global cost of 37 million euros. In addition to Messi, the founding donors of the center are: Fundación Barça, Maria Àngels Recolons Morer, Stavros Niarchos Foundation, Fundación La Caixa, Esteve, Andbank, Atrys, Fundació Nou Mil·lenni, Asociación Benéfica Anita, Fundación Joan Ribas Araquistain, Rosalia Gispert Barral, Invest for Children, Roman Rosell Dolset and the families and patient associations. More than 150 companies and entities also contributed to making the PCCB a reality with their contributions. Most of these collaborators are represented on the Donor Wall installed in the main lobby of the new center.
--- What is the center's annual budget?
--- The research laboratory budget for the center for this year is approximately 3.8 million euros, and 65% of it depends on private donations. Our largest donors are international, and that is because the center's vocation is to be able to attract patients from all over the world. And it is already happening, 35% of our patients are international, something unique in Europe.
--- What is on your horizon of objectives?
--- In the next 10 years, we would like to reach 85% cure rate for all childhood cancers. It is a very ambitious goal, but we have achieved more difficult things. If on the day of the inauguration of this center (June 16, 2022) we celebrated that it was a reality thanks to the donation of many people, a satisfaction that was felt greatly that day, we also committed to culminate the project with the ambition that someday everyone will be cured. We want to believe that with our model it is possible to achieve it.