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

Nikolas G Balanis1, Katherine M Sheu1, Favour N Esedebe1

  • 1Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA 90095, USA.

Cancer Cell
|July 10, 2019
PubMed

Insights

Small-cell neuroendocrine cancers (SCNCs) can arise in many epithelial cancers, presenting a poor prognosis. These cancers share vulnerabilities with hematological malignancies, suggesting broader treatment strategies.

Area of Science:

  • Oncology
  • Cancer Biology
  • Genetics

Background:

  • Small-cell neuroendocrine cancers (SCNCs) are aggressive and can emerge as a resistance mechanism to targeted therapies.
  • Transdifferentiation towards a small-cell neuroendocrine phenotype is a known route for cancer cells to evade treatment.

Purpose of the Study:

  • To investigate the prevalence and implications of a convergent small-cell neuroendocrine cancer state across various epithelial cancers.
  • To identify shared vulnerabilities and potential therapeutic targets in these convergent cancers.

Main Methods:

  • Analysis of gene expression data to identify SCN-associated transcription factors in primary tumors and metastases.
  • Drug sensitivity and gene dependency screens to uncover common vulnerabilities in SCN-like cancers.

Main Results:

  • A convergent small-cell neuroendocrine cancer state is widespread across epithelial cancers and linked to poor outcomes.
  • Metastases exhibit higher expression of SCN-associated transcription factors compared to primary tumors.
  • Convergent SCNCs, including unannotated SCN-like and small-round-blue cell tumors, share vulnerabilities with hematological malignancies.

Conclusions:

  • The convergent small-cell neuroendocrine phenotype represents a common pathway in epithelial cancers with significant prognostic implications.
  • Identified shared vulnerabilities between SCNCs and hematological cancers offer novel therapeutic avenues beyond tissue-specific treatments.
Keywords:
Dependency Map (depmap)RNA interference screenSCLCTCGAblood cancerdrug sensitivity screenpan-cancer signaturespharmacogenomicssmall-cell neuroendocrinetransdifferentiation

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