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Dose response curve



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Dose response curve 100 50 0 IC50 EC50 Dose Growth of Tumor Xenografts in Mice after Drug Treatment 22 Days MEK Inhibitor 22 Days Vehicle Control Primary tumor sections DAPI P H3 DAPI P ERK L3 6pl w o MEK inhibitor CK19 CK19 L3 6pl DAPI P H3 DAPI P ERK with MEK inhibitor CK19 CK19 Drug Sensitivities IC50 values of CI 1040 for 22 pancreatic cancer cell lines were measured The cell lines rank from sensitive to resistant low IC50 sensitive high IC50 resistant Why is that important to know Patients show often various degrees of sensitivities to drugs It would not be smart to treat a patient with a drug if he is not sensitive enough side effects It would be good to have a knowledge about drug sensivities of a patient in advance How can we get such a knowledge measuring biomarkers for drug sensitivities gene expression profiling comparative genomic hybridization proteomics Binding of a strand of DNA to a complementary strand of DNA or RNA Adenine binds to Thymine Guanine binds to Cytosine In RNA Thymine is replaced by Uracil The binding or annealing of complementary strands is highly sequence specific Microarray technology Examples Gene expression profiling Array based comparative genomic hybridization aCGH Array CGH aCGH a microarray based technology Human chromosomes become fragmentized Reference DNA isolated from control Cy5 Test DNA isolated from cancer cells Cy3 gain in the test DNA loss in the test DNA balanced in the test DNA DNA fragments become spotted on glass slide Image CCD camera and data analysis using software Example of an aCGH profile Array contains roughly 2500 printed DNA fragments covering the human genome at 1 4 Mbp resolution Log2 Mean Raw Ratio 1 2 5 3 5 7 9 11 13 15 17 19 21X Panc 4 21 1 5 0 5 0 5 1 5 Ratio 0 Tumor DNA is overrepresented gain in copy number amplifications Ratio 0 Tumor DNA is underrepresented loss in copy number deletions Combining drug sensitivities with array CGH We have measured copy number changes in 22 cell lines We also



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