The importance of basic and translational research in caring for children with malignant solid tumors in Latin America.

Objective: Basic and translational research in pediatric cancer are essential to improve patient care. To critically assess the developments achieved in these areas in Latin America, we systematically reviewed information published between 2013 and 2023. Methods: Studies of basic and translational research performed by investigators in Latin America evaluating pediatric malignant solid and central nervous system tumors were retrieved from PubMed. Original articles published in English between 2013 and 2023 were included. Collaborations among Latin American authors or among Latin American authors working with researchers from other continents were also included. Studies were excluded if they focused only on adults or on basic research in tumor biology not specifically related to the tumor types analyzed in this review. Results: A total of 550 articles were retrieved, but after removal of duplicates, 514 articles were included in the analysis, the majority of which were authored by researchers affiliated with institutions in Argentina, Brazil and Mexico. These countries also had the highest number of collaborations on original articles published with authors from Europe and North America. Argentina had the highest number of collaborations on original publications, with coauthors from Brazil and Uruguay. The median impact factor of the 244 journals in which articles were published was 3.5. The most commonly studied tumors were osteosarcomas, neuroblastomas and medulloblastomas; the most commonly studied areas were molecular analysis, tumor cell biology and biomarkers. Conclusions: In Latin America, research in pediatric oncology is on the agenda, despite a notable disparity in publication rates and frequency of collaboration between countries. There is a need to strengthen scientific collaboration within Latin America and with countries from other continents to promote research and to develop novel treatment strategies that reflect the local needs of children in Latin America who have solid tumors and brain cancer.

The importance of basic and translational research in caring for children with malignant solid tumors in Latin America / La importancia de la investigación básica y aplicada para la atención de pacientes pediátricos con tumores sólidos malignos en América Latina / A importância da pesquisa básica e translacional no tratamento de crianças com tumores sólidos malignos na América Latina

ABSTRACT Objective. Basic and translational research in pediatric cancer are essential to improve patient care. To critically assess the developments achieved in these areas in Latin America, we systematically reviewed information published between 2013 and 2023. Methods. Studies of basic and translational research performed by investigators in Latin America evaluating pediatric malignant solid and central nervous system tumors were retrieved from PubMed. Original articles published in English between 2013 and 2023 were included. Collaborations among Latin American authors or among Latin American authors working with researchers from other continents were also included. Studies were excluded if they focused only on adults or on basic research in tumor biology not specifically related to the tumor types analyzed in this review. Results. A total of 550 articles were retrieved, but after removal of duplicates, 514 articles were included in the analysis, the majority of which were authored by researchers affiliated with institutions in Argentina, Brazil and Mexico. These countries also had the highest number of collaborations on original articles published with authors from Europe and North America. Argentina had the highest number of collaborations on original publications, with coauthors from Brazil and Uruguay. The median impact factor of the 244 journals in which articles were published was 3.5. The most commonly studied tumors were osteosarcomas, neuroblastomas and medulloblastomas; the most commonly studied areas were molecular analysis, tumor cell biology and biomarkers. Conclusions. In Latin America, research in pediatric oncology is on the agenda, despite a notable disparity in publication rates and frequency of collaboration between countries. There is a need to strengthen scientific collaboration within Latin America and with countries from other continents to promote research and to develop novel treatment strategies that reflect the local needs of children in Latin America who have solid tumors and brain cancer.

RESUMEN Objetivo. La investigación básica y aplicada en el campo de la oncología pediátrica es fundamental para mejorar la atención al paciente. Con el objetivo de realizar una evaluación crítica de los avances logrados en este campo en América Latina, hemos realizado una revisión sistemática de la información publicada entre el 2013 y el 2023. Metodología. Se recopilaron de PubMed los artículos de investigación básica y traslacional publicados por investigadores de América Latina en los que se evaluaron tumores malignos sólidos y del sistema nervioso central en la población infantil. Se incluyeron artículos originales publicados en inglés entre el 2013 y el 2023. También se incluyeron artículos fruto de la colaboración científica entre autores e investigadores de América Latina y otros continentes. Se excluyeron aquellos estudios que se centraron solo en personas adultas o en la investigación básica en biología tumoral no relacionada específicamente con los tipos de tumores analizados en esta revisión. Resultados. Se encontraron 550 artículos en total. Después de eliminar los artículos duplicados, se incluyeron 514 artículos en la revisión, la mayoría de los cuales fueron escritos por investigadores vinculados a centros de investigación de Argentina, Brasil y México. También procedieron de estos tres países la mayor parte de los artículos originales escritos en colaboración con autores de Europa y América del Norte. Argentina tuvo el mayor número de colaboraciones en publicaciones originales, con coautores de Brasil y Uruguay. La mediana del índice de impacto de las 244 revistas en las que se publicaron los artículos fue de 3,5. Los tumores más estudiados fueron osteosarcomas, neuroblastomas y meduloblastomas. Los temas más estudiados fueron el análisis molecular, la biología de las células tumorales y los biomarcadores. Conclusiones. La investigación en oncología pediátrica forma parte de la agenda de investigación de América Latina, si bien hay una disparidad notoria en las tasas de publicación y la frecuencia de la colaboración entre países. Es necesario fortalecer la colaboración científica dentro de América Latina y con los países de otros continentes para promover la investigación y desarrollar estrategias de tratamiento novedosas que respondan a las necesidades locales de los niños y niñas de América Latina que tienen tumores sólidos o cáncer del sistema nervioso central.

RESUMO Objetivo. A pesquisa básica e translacional em câncer pediátrico é essencial para melhorar o atendimento dos pacientes. No intuito de realizar uma avaliação crítica dos avanços alcançados nessa área na América Latina, fez-se uma revisão sistemática de informações publicadas entre 2013 e 2023. Métodos. Pesquisas básicas e translacionais realizadas por pesquisadores da América Latina que avaliaram tumores sólidos malignos e tumores do sistema nervoso central em crianças foram obtidas da base de dados PubMed. Foram incluídos artigos originais publicados em inglês entre 2013 e 2023. Também foram incluídas colaborações entre autores latino-americanos ou entre autores latino-americanos que trabalham com pesquisadores de outros continentes. Estudos que tratavam apenas de adultos ou pesquisas básicas sobre biologia tumoral não especificamente relacionadas aos tipos de tumor analisados nesta revisão foram excluídos. Resultados. No total, a busca recuperou 550 artigos da base de dados. Após a remoção dos artigos duplicados, foram incluídos 514 artigos na análise, a maioria de autoria de pesquisadores de instituições da Argentina, do Brasil e do México. Esses países também tiveram o maior número de colaborações em artigos originais publicados com autores da Europa e da América do Norte. A Argentina teve o maior número de colaborações em publicações originais, com coautores do Brasil e do Uruguai. O fator de impacto mediano dos 244 periódicos nos quais os artigos foram publicados era de 3,5. Os tumores mais estudados foram osteossarcomas, neuroblastomas e meduloblastomas; as áreas mais estudadas foram análise molecular, biologia de células tumorais e biomarcadores. Conclusões. Na América Latina, a pesquisa em oncologia pediátrica está na ordem do dia, apesar de uma evidente disparidade nos índices de publicação e na frequência de colaboração entre os países. É necessário fortalecer a colaboração científica dentro da América Latina e com países de outros continentes a fim de promover a pesquisa e desenvolver novas estratégias de tratamento que reflitam as necessidades locais das crianças latino-americanas com tumores sólidos e câncer cerebral.

The importance of basic and translational research in caring for children with malignant solid tumors in Latin America / La importancia de la investigación básica y aplicada para la atención de pacientes pediátricos con tumores sólidos malignos en América Latina / A importância da pesquisa básica e translacional no tratamento de crianças com tumores sólidos malignos na América Latina

[ABSTRACT]. Objective. Basic and translational research in pediatric cancer are essential to improve patient care. To critically assess the developments achieved in these areas in Latin America, we systematically reviewed information published between 2013 and 2023. Methods. Studies of basic and translational research performed by investigators in Latin America evaluating pediatric malignant solid and central nervous system tumors were retrieved from PubMed. Original articles published in English between 2013 and 2023 were included. Collaborations among Latin American authors or among Latin American authors working with researchers from other continents were also included. Studies were excluded if they focused only on adults or on basic research in tumor biology not specifically related to the tumor types analyzed in this review. Results. A total of 550 articles were retrieved, but after removal of duplicates, 514 articles were included in the analysis, the majority of which were authored by researchers affiliated with institutions in Argentina, Brazil and Mexico. These countries also had the highest number of collaborations on original articles published with authors from Europe and North America. Argentina had the highest number of collaborations on original publications, with coauthors from Brazil and Uruguay. The median impact factor of the 244 journals in which articles were published was 3.5. The most commonly studied tumors were osteosarcomas, neuroblastomas and medulloblastomas; the most commonly studied areas were molecular analysis, tumor cell biology and biomarkers. Conclusions. In Latin America, research in pediatric oncology is on the agenda, despite a notable disparity in publication rates and frequency of collaboration between countries. There is a need to strengthen scientific collaboration within Latin America and with countries from other continents to promote research and to develop novel treatment strategies that reflect the local needs of children in Latin America who have solid tumors and brain cancer.

[RESUMEN]. Objetivo. La investigación básica y aplicada en el campo de la oncología pediátrica es fundamental para mejorar la atención al paciente. Con el objetivo de realizar una evaluación crítica de los avances logrados en este campo en América Latina, hemos realizado una revisión sistemática de la información publicada entre el 2013 y el 2023. Metodología. Se recopilaron de PubMed los artículos de investigación básica y traslacional publicados por investigadores de América Latina en los que se evaluaron tumores malignos sólidos y del sistema nervioso central en la población infantil. Se incluyeron artículos originales publicados en inglés entre el 2013 y el 2023. También se incluyeron artículos fruto de la colaboración científica entre autores e investigadores de América Latina y otros continentes. Se excluyeron aquellos estudios que se centraron solo en personas adultas o en la investigación básica en biología tumoral no relacionada específicamente con los tipos de tumores analizados en esta revisión. Resultados. Se encontraron 550 artículos en total. Después de eliminar los artículos duplicados, se incluyeron 514 artículos en la revisión, la mayoría de los cuales fueron escritos por investigadores vinculados a centros de investigación de Argentina, Brasil y México. También procedieron de estos tres países la mayor parte de los artículos originales escritos en colaboración con autores de Europa y América del Norte. Argentina tuvo el mayor número de colaboraciones en publicaciones originales, con coautores de Brasil y Uruguay. La mediana del índice de impacto de las 244 revistas en las que se publicaron los artículos fue de 3,5. Los tumores más estudiados fueron osteosarcomas, neuroblastomas y meduloblastomas. Los temas más estudiados fueron el análisis molecular, la biología de las células tumorales y los biomarcadores. Conclusiones. La investigación en oncología pediátrica forma parte de la agenda de investigación de América Latina, si bien hay una disparidad notoria en las tasas de publicación y la frecuencia de la colab- oración entre países. Es necesario fortalecer la colaboración científica dentro de América Latina y con los países de otros continentes para promover la investigación y desarrollar estrategias de tratamiento novedosas que respondan a las necesidades locales de los niños y niñas de América Latina que tienen tumores sólidos o cáncer del sistema nervioso central.

[RESUMO]. Objetivo. A pesquisa básica e translacional em câncer pediátrico é essencial para melhorar o atendimento dos pacientes. No intuito de realizar uma avaliação crítica dos avanços alcançados nessa área na América Latina, fez-se uma revisão sistemática de informações publicadas entre 2013 e 2023. Métodos. Pesquisas básicas e translacionais realizadas por pesquisadores da América Latina que avaliaram tumores sólidos malignos e tumores do sistema nervoso central em crianças foram obtidas da base de dados PubMed. Foram incluídos artigos originais publicados em inglês entre 2013 e 2023. Também foram incluídas colaborações entre autores latino-americanos ou entre autores latino-americanos que trabalham com pesqui- sadores de outros continentes. Estudos que tratavam apenas de adultos ou pesquisas básicas sobre biologia tumoral não especificamente relacionadas aos tipos de tumor analisados nesta revisão foram excluídos. Resultados. No total, a busca recuperou 550 artigos da base de dados. Após a remoção dos artigos duplicados, foram incluídos 514 artigos na análise, a maioria de autoria de pesquisadores de instituições da Argentina, do Brasil e do México. Esses países também tiveram o maior número de colaborações em artigos originais publicados com autores da Europa e da América do Norte. A Argentina teve o maior número de colaborações em publicações originais, com coautores do Brasil e do Uruguai. O fator de impacto mediano dos 244 periódicos nos quais os artigos foram publicados era de 3,5. Os tumores mais estudados foram osteossarcomas, neuroblastomas e meduloblastomas; as áreas mais estudadas foram análise molecular, biologia de células tumorais e biomarcadores. Conclusões. Na América Latina, a pesquisa em oncologia pediátrica está na ordem do dia, apesar de uma evidente disparidade nos índices de publicação e na frequência de colaboração entre os países. É necessário fortalecer a colaboração científica dentro da América Latina e com países de outros continentes a fim de pro- mover a pesquisa e desenvolver novas estratégias de tratamento que reflitam as necessidades locais das crianças latino-americanas com tumores sólidos e câncer cerebral.

Establishment and Comprehensive Characterization of a Novel Preclinical Platform of Metastatic Retinoblastoma for Therapeutic Developments.

Purpose: Although there have been improvements in the management of metastatic retinoblastoma, most patients do not survive, and all patients suffer from multiple short- and long-term treatment toxicities. Reliable and informative models to assist clinicians are needed. Thus we developed and comprehensively characterized a novel preclinical platform of primary cell cultures and xenograft models of metastatic retinoblastoma to provide insights into the molecular biology underlying metastases and to perform drug screening for the identification of hit candidates with the highest potential for clinical translation. Methods: Orbital tumor, bone marrow, cerebrospinal fluid, and lymph node tumor infiltration specimens were obtained from seven patients with metastatic retinoblastoma at diagnosis, disease progression, or relapse. Tumor specimens were engrafted in immunodeficient animals, and primary cell lines were established. Genomic, immunohistochemical/immunocytochemical, and pharmacological analysis were performed. Results: We successfully established five primary cell lines: two derived from leptomeningeal, two from orbital, and one from lymph node tumor dissemination. After the intravitreal or intraventricular inoculation of these cells, we established cell-derived xenograft models. Both primary cell lines and xenografts accurately retained the histological and genomic features of the tumors from which they were derived and faithfully recapitulated the dissemination patterns and pharmacological sensitivity observed in the matched patients. Conclusions: Ours is an innovative and thoroughly characterized preclinical platform of metastatic retinoblastoma developed for the understanding of tumor biology of this highly aggressive tumor and has the potential to identify drug candidates to treat patients who currently lack effective treatment options.