Supplemental data for Figure 4.

PDF file - 199KB, RNA was extracted from 18 human NSCLCs and 27 pancreatic directly xenografted low passage tumors. Levels of miR200c were measured by quantitative RT-PCR and mRNA levels of Mig6 and EGFR were determined by Affymetrix expression array. Expression levels of A. miR200c, B. Mig6 mRNA or C. EGFR mRNA transcripts were plotted against erlotinib responsiveness.

PDF file - 2120KB, FAK activity is significantly higher in erlotinib-resistant cells from lung and H and N origin. Total cell lysates were extracted from two pairs of lung (H358/H1703 and Calu3/Calu6) and two pairs of H and N (SCC-S/SCC-R and JHU011/JHU028) cancer cell lines and were subjected to immunoblot analysis with antibodies specific for phosphorylated and total FAK. Beta-actin was used a loading control.

AUC results of the drug sensitivity screens in conditionally reprogrammed PDAC cells.

Supplemental Figure 4. mRNA abundance in triptolide-treated PDAC 001 cells

Supplemental Figure 3. Testing screen hits in patient-derived xenografts.

PDF file - 38KB, Protocol for Avatar Generation.

Supplemental Figure 2. Rapid derivation of PDAC cells in culture.

PDF file - 127KB, Levels of Mig6 protein in the panel of 25 human cancer cell lines with known erlotinib resistance was identified by immunoblot analysis followed by densitometric quantification. The expression level of Mig6 was plotted against IC50 of corresponding cell line.

ERCC3 interacting proteins.

PDF - 75K, Normalized basal gene expression microarray data for non-squamous NSCLC NCI60 cell lines were grouped according to KRAS mutation status. Genes showing significant differences in expression between KRAS mutant and KRAS wildtype cells were analyzed using Ingenuity Pathway Analysis (IPA) and significantly different canonical pathways were identified.

Supplemental Figure 5. Quantified protein expression in PDAC 001 cells.

PDF file - 108KB, TGFbeta induces EMT-associated kinase switch promotes erlotinib-resistance of tumor cells. A. Erlotinib sensitive cell lines H292 and SCC-S were treated with TGFβ1 (4 ng/ml) for 21 days and immunoblot analysis was performed with indicated antibodies. B. Parental and TGFbeta-induced H358 and SCC-S cells were treated with erlotinib for 72 hours and cell viability was assayed. Values were set at 100% for untreated controls. C. Protein lysates were extracted from H358 and SCC-S cells treated or untreated with TGFbeta for 21 days and immunoblot analysis was performed with antibodies against indicated phospho RTKs. Beta-actin was used as a loading control.

PDF file - 127KB, Levels of Mig6 protein in the panel of 25 human cancer cell lines with known erlotinib resistance was identified by immunoblot analysis followed by densitometric quantification. The expression level of Mig6 was plotted against IC50 of corresponding cell line.

Supplemental Figure S1. Rapid derivation of PDAC cells in culture

PDF - 68K, Normalized basal gene expression microarray data for non-squamous NSCLC NCI60 cell lines were grouped according to KRAS mutation status. Genes showing significant differences in expression between KRAS mutant and KRAS wildtype cells were analyzed using Ingenuity Pathway Analysis (IPA) and significantly different upstream regulators were predicted.

PDF - 69K, Normalized basal gene expression microarray data for non-squamous NSCLC NCI60 cell lines were grouped according to KRAS mutation status. Genes showing significant differences in expression between KRAS mutant and KRAS wildtype cells were analyzed using Ingenuity Pathway Analysis (IPA) and genes predicted to be regulated by MYC were identified.

PDF file - 137KB, A. Mig6(mRNA)/miR200 ratios plotted on the linear scale. Each bar represents the Mig6(mRNA)/miR200 ratio of an indicated cell line. B. The exposure density of both EGFR and Mig6 blotted on the same membrane were quantified by densitometry and the values of Mig6/EGFR ration for every cell line were plotted on the linear scale.

PDF file - 802KB, Somatic mutations and Copy number variations.

Table S1. Genetic characterization of patient-derived xenografts using the Illumina Trusight panel capturing frequent mutations in 94 genes and 284 SNPs associated with cancer Table S3. Triptolide-induced effects on the mRNA abundance was determined by Illumina HighSeq RNA sequencing of 001 cells treated with 100 nM triptolide in vitro for 6 hours.