Pan-cancer Convergence to a Small-Cell Neuroendocrine Phenotype that Shares Susceptibilities with Hematological Malignancies.
Cancer Cell
; 36(1): 17-34.e7, 2019 07 08.
Article
em En
| MEDLINE
| ID: mdl-31287989
ABSTRACT
Small-cell neuroendocrine cancers (SCNCs) are an aggressive cancer subtype. Transdifferentiation toward an SCN phenotype has been reported as a resistance route in response to targeted therapies. Here, we identified a convergence to an SCN state that is widespread across epithelial cancers and is associated with poor prognosis. More broadly, non-SCN metastases have higher expression of SCN-associated transcription factors than non-SCN primary tumors. Drug sensitivity and gene dependency screens demonstrate that these convergent SCNCs have shared vulnerabilities. These common vulnerabilities are found across unannotated SCN-like epithelial cases, small-round-blue cell tumors, and unexpectedly in hematological malignancies. The SCN convergent phenotype and common sensitivity profiles with hematological cancers can guide treatment options beyond tissue-specific targeted therapies.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenótipo
/
Tumores Neuroendócrinos
/
Carcinoma de Células Pequenas
/
Neoplasias Hematológicas
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Cancer Cell
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos