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 language | English (US) |
|---|---|
| Pages (from-to) | 225-239 |
| Number of pages | 15 |
| Journal | Cancer Letters |
| Volume | 371 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 1 2016 |
| Externally published | Yes |
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Keywords
- Bromodomain inhibitors
- Hedgehog inhibitors
- SCLC
- SCLC gene expression
- Small cell lung cancer
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Bromodomain and hedgehog pathway targets in small cell lung cancer. / Kaur, Gurmeet; Reinhart, Russell A.; Monks, Anne; Evans, David; Morris, Joel; Polley, Eric; Teicher, Beverly A.
In: Cancer Letters, Vol. 371, No. 2, 01.01.2016, p. 225-239.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Bromodomain and hedgehog pathway targets in small cell lung cancer
AU - Kaur, Gurmeet
AU - Reinhart, Russell A.
AU - Monks, Anne
AU - Evans, David
AU - Morris, Joel
AU - Polley, Eric
AU - Teicher, Beverly A.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
KW - Bromodomain inhibitors
KW - Hedgehog inhibitors
KW - SCLC
KW - SCLC gene expression
KW - Small cell lung cancer
UR - http://www.scopus.com/inward/record.url?scp=84962019891&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84962019891&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2015.12.001
DO - 10.1016/j.canlet.2015.12.001
M3 - Article
C2 - 26683772
AN - SCOPUS:84962019891
VL - 371
SP - 225
EP - 239
JO - Cancer Letters
JF - Cancer Letters
SN - 0304-3835
IS - 2
ER -