A first-generation pediatric cancer dependency map.
Nat Genet
; 53(4): 529-538, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-33753930
ABSTRACT
Exciting therapeutic targets are emerging from CRISPR-based screens of high mutational-burden adult cancers. A key question, however, is whether functional genomic approaches will yield new targets in pediatric cancers, known for remarkably few mutations, which often encode proteins considered challenging drug targets. To address this, we created a first-generation pediatric cancer dependency map representing 13 pediatric solid and brain tumor types. Eighty-two pediatric cancer cell lines were subjected to genome-scale CRISPR-Cas9 loss-of-function screening to identify genes required for cell survival. In contrast to the finding that pediatric cancers harbor fewer somatic mutations, we found a similar complexity of genetic dependencies in pediatric cancer cell lines compared to that in adult models. Findings from the pediatric cancer dependency map provide preclinical support for ongoing precision medicine clinical trials. The vulnerabilities observed in pediatric cancers were often distinct from those in adult cancer, indicating that repurposing adult oncology drugs will be insufficient to address childhood cancers.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Regulação Neoplásica da Expressão Gênica
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Genoma Humano
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Mapeamento Cromossômico
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Mutação
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Proteínas de Neoplasias
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Neoplasias
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article