Bromodomain and hedgehog pathway targets in small cell lung cancer

Gurmeet Kaur, Russell A. Reinhart, Anne Monks, David Evans, Joel Morris, Eric Polley, Beverly A. Teicher

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Small cell lung cancer (SCLC) is an extremely aggressive cancer that frequently recurs. Twenty-three human SCLC lines were selected representing varied Myc status. Gene expression of lung cancer, stem-like, hedgehog pathway, and notch pathway genes were determined by RT2-PCR array and Exon 1.0 ST array. Etoposide and topotecan concentration response was examined. The IC50's for etoposide and topotecan ranged over nearly 3 logs upon 96hrs exposure to the drugs. Myc status, TOP2A, TOP2B and TOP1 mRNA expression or topoisomerase 1 and topoisomerase 2 protein did not account for the range in the sensitivity to the drugs. γ-secretase inhibitors, RO429097 and PF-03084014, had little activity in the SCLC lines over ranges covering the clinical Cmax concentrations. MYC amplified lines tended to be more sensitive to the bromodomain inhibitor JQ1. The Smo antagonists, erismodegib and vismodegib and the Gli antagonists, HPI1 and SEN-450 had a trend toward greater sensitivity of the MYC amplified line. Recurrent SCLC is among the most recalcitrant cancers and drug development efforts in this cancer are a high priority.

Original languageEnglish (US)
Pages (from-to)225-239
Number of pages15
JournalCancer Letters
Volume371
Issue number2
DOIs
StatePublished - 2016

Keywords

  • Bromodomain inhibitors
  • Hedgehog inhibitors
  • SCLC
  • SCLC gene expression
  • Small cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kaur, G., Reinhart, R. A., Monks, A., Evans, D., Morris, J., Polley, E., & Teicher, B. A. (2016). Bromodomain and hedgehog pathway targets in small cell lung cancer. Cancer Letters, 371(2), 225-239. https://doi.org/10.1016/j.canlet.2015.12.001