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03/04/2019

Researchers at VHIR identify a new therapeutic tool based on microRNAs against a type of childhood cancer

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03/04/2019

The results of the study provide a proof of concept of the usefulness of this type of therapeutic strategies for neuroblastoma and other types of childhood cancer.

Researchers from the http://en.vhir.org/portal1/grup-equip.asp?s=recerca&contentid=186749 Translational Research in Child and Adolescent Cancer group at the Vall d'Hebron Research Institute (VHIR) have identified new microRNAs capable of reducing the growth of tumor cells of neuroblastoma, a type of childhood cancer. The results of the work, published in https://link.springer.com/article/10.1007/s00018-019-03041-4 Cellular and Molecular Life Sciences, provide the basis for the development of new therapies based on microRNA for the treatment of more aggressive neuroblastomas.In Europe, about 15,000 new cases of pediatric cancer are diagnosed annually, and about 10% correspond to neuroblastoma, an embryonic tumor of the sympathetic nervous system. The coordinators of the group, Dr. Soledad Gallego and Dr. Josep Sánchez de Toledo state that "survival is excellent in patients with low-risk neuroblastoma, but that it is below 50% among high-risk patients, and therefore, the development of new therapies is necessary ".One of the main lines of research of the group, led by Dr. Miguel Segura, has as its main objective to develop epigenetic therapies, which are those aimed at modulating the expression of genes but without changing the sequence of the genome. Within this emerging field, special attention is paid to the therapeutic use of microRNAs, small RNA molecules capable of regulating multiple genes and signaling pathways at the same time, minimizing the appearance of resistance mechanisms to therapy.In order to identify the microRNAs with the greatest therapeutic potential in neuroblastoma, the researchers performed a high-throughput screening by restoring the expression of 2048 microRNAs in tumor cells of neuroblastoma. According to the main authors of the study, Dr. Aroa Soriano and the researcher Marc Masanas, this strategy allowed the identification of miR-323a-5p and miR-342-5p as tumor growth supressors in cellular and animal models "."The results of the study provide us with a proof of concept of the usefulness of this type of therapeutic strategies based on the restoration of the expression of microRNAs as a new treatment for neuroblastoma as well as for other types of pediatric cancer," explains Dr. Soriano. "We have seen that miR-323a-5p and miR-342-5p have the potential to regulate multiple therapeutic targets related to the cell cycle and the survival of tumors," says Marc Masanas. "In addition, the combination of inhibitors targeting genes regulated by microRNAs such as CCND1, CHAF1A, INCENP and BCL-XL could also be investigated as a new therapeutic strategy for high-risk neuroblastomas," reiterate the researchers.The next step of this study is to make the treatment based on microRNAs a reality. "A barrier that we find is that the application of these new treatments is limited by the lack of adequate clinical formulations that protect, stabilize and lead these molecules to tumors," explains Dr. Segura, the group's principal investigator. For this reason, the researchers are working in a multidisciplinary way with experts in nanoparticles (Grupo Nanomol-ICMAB-CSIC) to - in the future - be able to administer the microRNAs identified in the study for the treatment of high-risk neuroblastoma.The study has been funded by the Instituto Carlos III, the Marie Curie program of the European Community, the Ministry of Education, Culture and Sports, the Spanish Association against Cancer (AECC) and the Associations Acunapatata and Asociación NEN.

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