Pan-cancer Convergence to a Small-Cell Neuroendocrine Phenotype that Shares Susceptibilities with Hematological Malignancies.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Balanis, NG; Sheu, KM; Esedebe, FN; Patel, SJ; Smith, BA; Park, JW; Alhani, S; Gomperts, BN; Huang, J; Witte, ON; Graeber, TG

Published Date

  • July 8, 2019

Published In

Volume / Issue

  • 36 / 1

Start / End Page

  • 17 - 34.e7

PubMed ID

  • 31287989

Pubmed Central ID

  • PMC6703903

Electronic International Standard Serial Number (EISSN)

  • 1878-3686

Digital Object Identifier (DOI)

  • 10.1016/j.ccell.2019.06.005


  • eng

Conference Location

  • United States