Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage.

Journal Article (Journal Article)

The use of potent therapies inhibiting critical oncogenic pathways active in epithelial cancers has led to multiple resistance mechanisms, including the development of highly aggressive, small cell neuroendocrine carcinoma (SCNC). SCNC patients have a dismal prognosis due in part to a limited understanding of the molecular mechanisms driving this malignancy and the lack of effective treatments. Here, we demonstrate that a common set of defined oncogenic drivers reproducibly reprograms normal human prostate and lung epithelial cells to small cell prostate cancer (SCPC) and small cell lung cancer (SCLC), respectively. We identify shared active transcription factor binding regions in the reprogrammed prostate and lung SCNCs by integrative analyses of epigenetic and transcriptional landscapes. These results suggest that neuroendocrine cancers arising from distinct epithelial tissues may share common vulnerabilities that could be exploited for the development of drugs targeting SCNCs.

Full Text

Duke Authors

Cited Authors

  • Park, JW; Lee, JK; Sheu, KM; Wang, L; Balanis, NG; Nguyen, K; Smith, BA; Cheng, C; Tsai, BL; Cheng, D; Huang, J; Kurdistani, SK; Graeber, TG; Witte, ON

Published Date

  • October 5, 2018

Published In

Volume / Issue

  • 362 / 6410

Start / End Page

  • 91 - 95

PubMed ID

  • 30287662

Pubmed Central ID

  • PMC6414229

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.aat5749


  • eng

Conference Location

  • United States