Lack of biomarkers and high prevalence of congenital tumors limit the progress of precision medicine in pediatric oncology.

There has been considerable progress in the treatment of cancer patients in recent years. One of these has been so-called precision medicine. However, although it is destined to be a revolution, it is still an emerging approach in some areas today. Pediatric oncology presents various challenges, primarily arising from the few therapeutic targets for tumors in children that have been discovered to date.

To apply this precise medicine, it is necessary to take into account the individual variability of genes, environment and lifestyle of each patient. Precision medicine involves detailed genomic profiling of tumors, in this case pediatric tumors. This involves analyzing specific genetic changes in the tumor’s DNA to identify mutations, gene fusions or other genomic abnormalities that may make it susceptible. targeted treatment,

In this sense, as explained in the Gaeta Medica Luis Madero, head of the oncohematology and transplant service at the Niño Jesus University Children’s Hospital in Madrid, “Very few mutations or specific targets have been found in childhood cancers. However, for those that exist, there is no doubt that it is the best option they have. Experts explain that “some targets are genetic alterations ALK for neuroblastoma or BRAF for low-grade astrocytoma. In cases where there are no specific target options in both medical oncology and pediatric oncology, other disorders have been sought for which there are other drugs, such as tyrosine kinase inhibitors.

targeted treatment

Based on genomic information, targeted therapies designed to act on specific changes found in tumors can be identified. These treatments are designed to be more effective and specific while reducing side effects compared to traditional treatments. As with any drug treatment, clinical trials are necessary, however, since pediatric cancers are less common than adult cancers, precision medicine in this area often includes a close cooperation between researchers, pediatric oncologists, geneticists and drug development experts.

Luis Madero is head of the oncohematology and transplant service at the Niño Jesus University Children’s Hospital in Madrid.

“The first thing that is done is a preclinical study in phase I, then phase II is usually done in adult solid tumors such as breast cancer, lung cancer, prostate adenocarcinoma, etc., that is, in pathologies that only affect adults. Does, explains Madero. “Once the mutation is detected in these adult tumors, it is tested in other childhood malignancies Check if it is effective too, This opens up the possibility of conducting adequate clinical trials, which will lead to the development of targeted drugs that can be used in pediatric diseases.

Limited Biomarkers

Although Detection of oncological biomarkers in pediatric populations is limited Due to various factors. On the one hand, pediatric oncological pathology occurs much less frequently than in adults, which leads to less research and a smaller number of specific biomarkers identified. Furthermore, as experts point out, “the pharmaceutical industry looks for signs of very prevalent pathology. The point is that many children with tumors are cured 80 percent of the time, so they don’t ‘need’ much from conventional therapy and the industry generally doesn’t bet on it.”

Furthermore, another complication faced in this field is that the mutation load required for these treatments to be high is not the case in the case of congenital pediatric tumors, which constitute a large percentage. “It should be noted that many pediatric patients present with what are called cold tumorsThat is, they have much lower amounts of lymphocytes infiltrating within the tumor and this may lead to the response to these treatments not being as favorable,” the oncologist explains.

questions to ask

The recent study, ‘Precision Medicine for Childhood Cancer: Current Limits and Future Perspectives’, published in the JCO Precision Oncology Journal, explains Current Implementation Limitations Of precision medicine in pediatric oncology.

The publication highlights that it is essential Pool existing large data sets and perform standardized analysis, This highlights initiatives such as the European ITCC Big Data 23 project and the University of Chicago Pediatric Cancer Data Commons that are already taking steps to achieve international standardization in the processing and analysis of clinical and molecular data. On the other hand, it also points to the importance of development international consensusOn the applicability definitions used in all data sets, based on empirical data.

Reporting of outcomes should be standardized and made routine to allow meaningful comparisons between patient groups. Furthermore, the most accurate, efficient and cost-effective technologies should be agreed upon which will be routinely implemented.

Along similar lines, studies show Result reporting should also be standardized and made routine Allowing meaningful comparisons between patient groups. Furthermore, it must Agree on the most accurate, efficient and profitable technologies Which will be implemented regularly. Finally, the document indicates that there is an urgent need Develop clinical trial designs capable of robustly evaluating added valueIncluding the impact on survival of molecular abnormalities and precision medicine therapies for children across the full range of childhood cancers. Furthermore, the study itself states that “Given the rarity of many molecular alterations and the possibility that response to targeted agents may vary by specific tumor type, these trials will require extensive collaboration.”

current point of investigation

Despite the complexity of the discovery of specific biomarkers in oncology, especially in the field of pediatric oncology, currently Research is open to all tumors In other aspects. “Many pediatric trials are being conducted in all types of cancers, but the focus is not on finding specific mutations. For example, in the case of childhood congenital fibrosarcoma, the mechanism of action has been found. That is, all tumors that have the same pathway, in this case, can benefit from NTRK inhibitors,” explains Madero, who clarifies that “these drugs are not approved because they have a specific biomarker, but rather. So that they target the mechanism of action”.

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