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

Publication date: 8 July 2019Source: Cancer Cell, Volume 36, Issue 1Author(s): Nikolas G. Balanis, Katherine M. Sheu, Favour N. Esedebe, Saahil J. Patel, Bryan A. Smith, Jung Wook Park, Salwan Alhani, Brigitte N. Gomperts, Jiaoti Huang, Owen N. Witte, Thomas G. GraeberSummarySmall-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.Graphical Abstract

Source: Cancer Cell - July 9, 2019 Category: Cancer & Oncology Source Type: research