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. Author manuscript; available in PMC: 2017 Feb 28.

Published in final edited form as: Cancer Lett. 2015 Dec 10;371(2):225–239. doi: 10.1016/j.canlet.2015.12.001

PANEL A Expression of genes associated with the Hedgehog pathway in 23 SCLC lines as determined by the 1/ΔCT value from RT-PCR or as log2 from gene expression derived from exon arrays. The blue symbols represent c-MYC amplified SCLC lines (n = 5), green symbols represent n-MYC amplified SCLC lines (n = 3), red symbols represent l-MYC amplified SCLC lines (n = 5) and gray symbols represents MYC unamplified SCLC lines (n = 10). PANEL B: Concentration response curves for the 23 SCLC lines exposed to 0.01 – 100 uM of the Gli inhibitors, HPI1 and SEN-450, and the Smo inhibitors, erismodegib and vismodegib, for 96 h. The blue symbols represent c-MYC amplified SCLC lines (n = 5), green symbols represent n-MYC amplified SCLC lines (n = 3), red symbols represent l-MYC amplified SCLC lines (n = 5) and gray symbols represents MYC unamplified SCLC lines (n = 10). The dotted lines are the clinical Cmax for erismodegib and vismodegib. The experiments were repeated 3–4 times. PANEL C: Concentration response curves for 4 representative SCLC lines exposed to 0.01 – 20 uM of erismodegib or vismodegib alone (blue line) or in simultaneous combination with 3.7uM carboplatin and 0.3uM etoposide (red line). The gray line is calculated simple Bliss additivity for the combination regimen.

PANEL A Expression of genes associated with the Hedgehog pathway in 23 SCLC lines as determined by the 1/ΔCT value from RT-PCR or as log2 from gene expression derived from exon arrays. The blue symbols represent c-MYC amplified SCLC lines (n = 5), green symbols represent n-MYC amplified SCLC lines (n = 3), red symbols represent l-MYC amplified SCLC lines (n = 5) and gray symbols represents MYC unamplified SCLC lines (n = 10). PANEL B: Concentration response curves for the 23 SCLC lines exposed to 0.01 – 100 uM of the Gli inhibitors, HPI1 and SEN-450, and the Smo inhibitors, erismodegib and vismodegib, for 96 h. The blue symbols represent c-MYC amplified SCLC lines (n = 5), green symbols represent n-MYC amplified SCLC lines (n = 3), red symbols represent l-MYC amplified SCLC lines (n = 5) and gray symbols represents MYC unamplified SCLC lines (n = 10). The dotted lines are the clinical Cmax for erismodegib and vismodegib. The experiments were repeated 3–4 times. PANEL C: Concentration response curves for 4 representative SCLC lines exposed to 0.01 – 20 uM of erismodegib or vismodegib alone (blue line) or in simultaneous combination with 3.7uM carboplatin and 0.3uM etoposide (red line). The gray line is calculated simple Bliss additivity for the combination regimen.