Lucas Moreno, oncologist: “Pharmaceutical companies are not showing much interest in childhood cancer” | Health and wellness

Childhood cancer, whose World Day is celebrated today, Thursday, has little in common with adult tumors. In both cases there are cells that go crazy and begin to multiply uncontrollably, but these are very different diseases: their origin is different, as is their frequency. “Fortunately,” says pediatric oncologist Lucas Moreno (Menorca, 45), childhood cancer affects only a few patients. “For every 200 adults, there is one childhood cancer. It is a disease of a minority, or rather a group of diseases, because there is not just one type of cancer, but 40 types,” explains this doctor, head of the department of pediatric oncology and hematology at the Vall d’Hebron hospital in Barcelona.

Moreno acknowledges that it is the low incidence of cases that makes the investigation difficult and that progress is being made gradually. An oncologist just published in a journal Journal of Clinical Oncology study in which they show that an innovative combination of drugs shows small improvements in children with very aggressive neuroblastoma. When there is no cure, the main thing is to gain time.

Ask. Why do childhood tumors appear? Experts say that in adults, if we improve our lifestyle, we can prevent 40% of tumors.

Reply. Childhood cancers are completely different and are not influenced by environmental factors. These are developmental changes: during embryonic development, some cells remain that do not function well, and at some point they begin to grow.

TO. Is childhood cancer still a big unknown?

R. The low frequency makes it difficult to explore, extract resources and collect the necessary data. Over the past decade there have been very important advances in knowledge about what happens to tumors. No reason has been identified that causes this, but it has been established what happens to their growth. But there are not many examples of the success of new drugs, as happened in oncology in adults.

TO. Is the process of cancer the same as in adults?

R. What ends up happening is crazy cell proliferation. What triggers it, we still don’t know, but what starts to happen, yes: in adult cancer, environmental factors cause mutations to accumulate, cells break down, and when they reach a certain level, they begin to grow. There are few mutations in childhood tumors; Most of all there are chromosomal changes, things on a larger scale, as well as the epigenome, which is not so much the sequence of DNA, but how it folds, how they connect…

TO. Can these changes be reversed or anticipated?

R. Not yet, because these environmental factors are unknown. There are also no population screening programs because these are tumors that grow very quickly. One area we are growing in is the 10% of cancers that are associated with some genetic characteristic that makes it easier for a tumor to develop: once these genes are identified, the whole family is tested so that if cancer occurs, it will be found. more clearly.

“80% of children with cancer are cured, but many have to live with the consequences.”

TO. What is the usual prognosis?

R. The most common types of cancer in children and adolescents are leukemia, lymphoma, and brain tumors. For cancer overall, survival outcomes are good, with more than 80% curable. But of that 80%, many have to live with the consequences of the treatment they receive, which affects their quality of life.

TO. What consequences?

R. For example, a patient who has a bone tumor and needs a hip or knee prosthesis: Living with a prosthesis your whole life creates a number of limitations in your life. Another example: Radiation therapy to the brain at a young age can affect your neurodevelopment, your learning, your performance at school… and in other parts of the body it can cause a new tumor 10 or 20 years later. There are patients who undergo cancer treatment and have absolutely no consequences and return to normal life without problems. But there are others who are exposed to this risk throughout their lives.

TO. You have explained the global forecast, but where is the light and shadow?

R. The best results are given by leukemia, lymphomas and some kidney tumors, the cure rate of which exceeds 90%, and in these cases the most important thing now is to improve the treatment as much as possible so that there are fewer consequences. On the other hand, there are other examples, such as brain tumors such as high-grade gliomas, and solid tumors such as some sarcomas and neuroblastomas, especially when metastatic, in which we do not cure even half of the patients. . The challenge here is to look for new drugs to improve these results.

TO. For neuroblastoma, they just got positive results from a trial combining chemotherapy with monoclonal antibodies.

R. This is a clinical trial of high-risk neuroblastoma, which metastasizes upon relapse. We’re trying all the new options that are available, and we’re trying monoclonal antibodies that prevent the growth of blood vessels that carry food to the tumor. We publish that it has improved response, that patients’ tumors have shrunk, or that patients are tumor-free for longer. Less than 10% of neuroblastoma patients who relapse survive. This is a very persistent disease.

TO. In this study, they said the response rate was 26% using the new therapeutic approach compared to 18% using chemotherapy alone. How is this data interpreted?

R. This disease is so persistent, and yet so many things have been tried so many times, that any small improvement allows children to live longer without recurrence of the disease. If this works a little and we add another combination to it in the next trial and it also improves, we will gradually achieve that improvement.

TO. What are the biggest challenges in finding a treatment that will reverse the disease?

R. One of them is the biology of the tumors, since they are very aggressive and do not respond to anything. The fact that it occurs in a small number of patients makes drug testing difficult. Additionally, childhood cancer is an area in which pharmaceutical companies have not shown much interest due to its rarity. There are now incentives and obligations for companies that work in the childhood cancer space, and there are more and more of them, but the volume as in adults is still small.

TO. In adults, there has been a revolution in the last decade with the advent of new medications. What is the situation with the therapeutic arsenal in children?

R. This huge explosion of precision oncology and immunotherapy in adults has not been reflected in childhood cancer. We don’t have that many drugs yet. Many have been tried and don’t work; and others have not yet arrived. Despite all those approved for adults, we can count on one hand the new drugs available for children.

TO. Was the great revolution of recent years CAR-T (cell therapy that involves taking T cells from a patient’s body, modifying them in the laboratory using genetic engineering, and returning them to the patient so they can better fight the tumor)?

R. The great revolution until the previous decade was to combine and make the most effective use of already available treatments (chemotherapy, radiation therapy and surgery). CAR-Ts are designed to fill specific gaps in specific diseases where they have truly changed the paradigm. Today, only one CAR-T is available for leukemia in a given situation, and there the results have changed. But there are no CAR-Ts for solid tumors, for other hematological tumors… They have not yet changed the paradigm of all pediatric oncology, but in specific situations where they play a very important role.

“Environmental factors do not influence childhood cancer; These are developmental disorders.”

TO. What cooking will shape the future of therapy?

R. There’s a big movement right now to produce CAR-Ts that have value in childhood cancers because they go against the targets that these tumors actually have. It’s still early, but we have high hopes because there will be many clinical trials in various applications in brain tumors, neuroblastomas, leukemia and other situations… And among all this, we think there will be revolutions.

TO. Where is gene therapy?

R. Gene therapy has not yet reached childhood cancer, but it has reached some hematologic diseases that can lead to childhood cancer. When a disease is caused by a gene stopping working, if there is a way to replace some cells with others in which the gene is fixed, it will correct your disease. In hematological diseases, this will result in patients having fewer cases of cancer. This will avoid collateral damage.

TO. What great unknowns remain to be solved in the field of childhood cancer?

R. It is very important to know what makes tumors resistant. Because we have first-line treatments for almost all tumors, but many of them become resistant and the cells escape. And we still don’t know how to prevent their persistence or block these mechanisms to prevent them from metastasizing and reappearing.

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