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Supplementary Data Supplementary Fig. 1 A B Responder_Xenograft_ Responder_Xenograft_ NON- NON- Lu7336, Vehicle vs Lu7466, Vehicle vs Responder_Xenograft_ Responder_Xenograft_ Sagopilone, Welch- Sagopilone, Welch- Lu7187, Vehicle vs Lu7406, Vehicle vs Test: 638 Test: 600 Sagopilone, Welch- Sagopilone, Welch- Test: 468 Test: 482 Responder_Xenograft_ NON- Lu7860, Vehicle vs Responder_Xenograft_ Sagopilone, Welch - Lu7558, Vehicle vs Test: 605 Sagopilone, Welch- Test: 333 Supplementary Fig. 2 Supplementary Fig. 3 Supplementary Figure S1. Venn diagrams comparing probe sets regulated by Sagopilone treatment (10mg/kg for 24h) between individual models (Welsh Test ellipse p-value<0.001 or 5-fold change). A Sagopilone responder models, B Sagopilone non-responder models. Supplementary Figure S2. Pathway analysis of genes regulated by Sagopilone treatment in responder xenograft models 24h after Sagopilone treatment by GeneGo Metacore; the most significant pathway map representing cell cycle/spindle assembly and chromosome separation is shown, genes upregulated by Sagopilone treatment are marked with red thermometers. Supplementary Figure S3. GeneGo Metacore pathway analysis of genes differentially expressed between Sagopilone Responder and Non-Responder models displaying –log(p-Values) of most significant pathway maps. Supplementary Tables Supplementary Table 1. Response and activity in 22 non-small-cell lung cancer (NSCLC) xenograft models after treatment with Sagopilone and other cytotoxic agents commonly used in the management of NSCLC Tumor Model Response type Sagopilone Carboplatin Paclitaxel Gemcitabine Lu7064 PLC R NR R NR Lu7126 SCC NR NR nt R Lu7166 LCC NR NR NR NR Lu7177 SCC R NR NR R Lu7187 PLC NR NR NR R Lu7198 ADC NR NR NR NR tox Lu7298 SCC R NR NR NR Lu7336 PLC R NR R R tox Lu7343 SCC R NR NR R Lu7387 ADC R NR R NR Lu7406 ADC NR NR NR NR Lu7414 SCC R NR NR NR Lu7433 SCC R R R NR Lu7462 ADC R NR NR R Lu7466 ADC R NR R R Lu7506 SCC R R R NR Lu7558 PLC NR R NR R Lu7612 SCC NR R R NR tox Lu7668 DDC R R R Tox Lu7700 ADC R NR NR R Lu7747 SCC NR NR NR NR Lu7860 SCC R NR R NR Overall response 14 (64%) 5 (23%) 9 (43%) 9 (43%) n (%) R, responder (tumor shrinkage and stable disease); NR, non-responder (tumor progression); nt, not tested; tox, toxic; ADC, adenocarcinoma; DDC, dedifferentiated carcinoma; LCC, large cell carcinoma; PLC, pleiomorphic carcinoma; SCC, squamous cell carcinoma Page 2 Supplementary Table 2. Genes regulated only in Sagopilone responder xenografts 24 hours after a single Sagopilone treatment at p<0.01 A Genes up-regulated after Sagopilone treatment Ratio of Ratio of P-Value: Means: P-Value: Means: Non- Non- Responde Respon Responde Responde r der r r Gene Entrez Xenograft Xenogr Xenograft Xenograft Probe-Set Symbol Gene Description Gene ID s afts s s hypothetical protein 1553736_at MGC23401 MGC23401 196441 2.24E-05 1.62 3.77E-01 1.10 205235_s_at MPHOSPH1 M-phase phosphoprotein 1 9585 1.35E-04 1.31 5.92E-01 1.06 210527_x_at TUBA2 tubulin, alpha 2 7278 4.47E-04 1.20 2.00E-02 1.18 hypothetical protein 225762_x_at LOC284801 LOC284801 284801 5.47E-04 1.39 3.55E-01 1.17 CDC20 cell division cycle 202870_s_at CDC20 20 homolog (S. cerevisiae) 991 6.42E-04 1.40 2.67E-02 1.29 202705_at CCNB2 cyclin B2 9133 7.76E-04 1.31 3.62E-02 1.18 214710_s_at CCNB1 cyclin B1 891 9.08E-04 1.42 2.27E-02 1.20 cyclin-dependent kinase inhibitor 3 (CDK2- associated dual specificity 209714_s_at CDKN3 phosphatase) 1033 1.07E-03 1.44 7.53E-01 1.05 chromosome 10 open 218542_at C10orf3 reading frame 3 55165 1.10E-03 1.28 4.47E-01 1.11 tubulin, alpha, ubiquitous, 211072_x_at K-ALPHA-1 tubulin, alpha, ubiquitous 10376 1.68E-03 1.10 2.58E-02 1.08 WW domain containing 242427_at WAC adaptor with coiled-coil 51322 1.85E-03 1.38 2.04E-01 1.11 NIMA (never in mitosis 204641_at NEK2 gene a)-related kinase 2 4751 2.05E-03 1.32 5.53E-02 1.21 chromosome 15 open 225300_at C15orf23 reading frame 23 90417 2.29E-03 1.30 1.92E-01 1.13 cyclin-dependent kinase inhibitor 3 (CDK2- associated dual specificity 1555758_a_at CDKN3 phosphatase) 1033 2.68E-03 1.39 7.04E-01 1.06 CDC28 protein kinase 204170_s_at CKS2 regulatory subunit 2 1164 2.72E-03 1.27 2.87E-01 1.12 cylicin, basic protein of 216809_at CYLC1 sperm head cytoskeleton 1 1538 2.81E-03 1.31 4.46E-01 0.88 226980_at DEPDC1B DEP domain containing 1B 55789 2.86E-03 1.37 6.34E-01 1.07 pituitary tumor-transforming 203554_x_at PTTG1 1 9232 3.43E-03 1.28 3.25E-01 1.11 204444_at KIF11 kinesin family member 11 3832 3.78E-03 1.21 8.85E-01 0.99 chromosome 8 open 227402_s_at C8orf53 reading frame 53 84294 3.97E-03 1.24 9.37E-02 1.13 218755_at KIF20A kinesin family member 20A 10112 4.11E-03 1.29 4.33E-02 1.16 zinc finger and BTB domain 226284_at ZBTB2 containing 2 57621 4.69E-03 1.14 2.30E-01 1.11 pituitary tumor-transforming 208511_at PTTG3 3 26255 4.91E-03 1.32 6.17E-01 1.06 gb:AI857685 227249_at /DB_XREF=gi:5511301 5.29E-03 1.26 9.60E-02 1.28 Page 3 /DB_XREF=wk96d11.x1 /CLONE=IMAGE:2423253 /FEA=EST /CNT=36 /TID=Hs.263925.3 /TIER=Stack /STK=24 /UG=Hs.263925 /LL=54820 /UG_GENE=FLJ20101 /UG_TITLE=LIS1- interacting ... translocase of inner mitochondrial membrane 9 218316_at TIMM9 homolog (yeast) 26520 5.37E-03 1.20 9.74E-01 1.00 discs, large homolog 7 203764_at DLG7 (Drosophila) 9787 5.75E-03 1.36 5.39E-01 1.12 1570528_at XYLT2 xylosyltransferase II 64132 5.79E-03 1.84 6.07E-01 0.86 centromere protein A, 204962_s_at CENPA 17kDa 1058 5.87E-03 1.34 1.79E-01 1.14 family with sequence 221591_s_at FAM64A similarity 64, member A 54478 5.95E-03 1.27 1.99E-01 1.13 trophinin associated protein 204649_at TROAP (tastin) 10024 6.24E-03 1.25 5.27E-02 1.16 chromosome 14 open 221907_at C14orf172 reading frame 172 115708 6.26E-03 1.19 8.89E-01 0.98 hypothetical protein 1559002_at LOC340544 LOC340544 340544 6.54E-03 1.20 7.05E-01 0.97 hypothetical protein 220060_s_at FLJ20641 FLJ20641 55010 6.58E-03 1.27 9.39E-01 1.01 209464_at AURKB aurora kinase B 9212 7.53E-03 1.26 8.50E-01 1.02 proline/serine-rich coiled- 201896_s_at PSRC1 coil 1 84722 7.67E-03 1.26 2.20E-01 1.12 Homo sapiens, clone 1569958_at IMAGE:4064953, mRNA 8.43E-03 1.75 7.66E-01 0.95 213599_at OIP5 Opa interacting protein 5 11339 8.84E-03 1.29 5.37E-01 1.07 gb:AL133269 /DB_XREF=gi:9662888 /FEA=DNA /CNT=1 /TID=Hs.302112.0 /TIER=ConsEnd /STK=0 /UG=Hs.302112 /UG_TITLE=Human DNA sequence from clone RP3- 468K3 on chromosome 6q25-26. Contains a beta 216475_at tubulin ... 8.97E-03 1.24 3.91E-01 1.09 218848_at WDR58 WD repeat domain 58 79228 9.16E-03 1.27 9.48E-01 1.01 209408_at KIF2C kinesin family member 2C 11004 9.23E-03 1.20 1.15E-01 1.14 209118_s_at TUBA3 tubulin, alpha 3 7846 9.36E-03 1.53 1.31E-01 1.55 238156_at RPS6 Ribosomal protein S6 6194 9.41E-03 1.27 4.39E-02 1.15 ELK4, ETS-domain protein 206919_at ELK4 (SRF accessory protein 1) 2005 9.86E-03 1.24 6.99E-01 0.92 Page 4 B Genes down-regulated after Sagopilone treatment Ratio of Ratio of P-Value: Means: P-Value: Means: Non- Non- Responde Respon Responde Responde Entrez r der r r Gene Gen Xenograft Xenogr Xenograft Xenograft Probe-Set Symbol Gene Description e ID s afts s s 241520_x_at KLHL15 Kelch-like 15 (Drosophila) 80311 1.90E-05 0.76 9.54E-01 1.01 Vitamin K epoxide reductase 238305_at VKORC1L1 complex, subunit 1-like 1 154807 6.06E-04 0.47 4.63E-01 0.83 Hypothetical gene supported 1558504_at LOC440721 by AK024248; AL137733 440721 1.09E-03 0.79 5.93E-01 1.06 POU domain, class 5, transcription factor 1, POU domain, class 5, transcription factor 1 pseudogene 1, similar to POU domain, class LOC441628 5, transcription factor 1 : POU5F1 : (Octamer-binding 441628, 210905_x_at POU5F1P1 transcription factor ... 5460, 5462 1.32E-03 0.57 2.88E-01 0.78 hypothetical protein 243047_at FLJ10404 FLJ10404 54540 1.37E-03 0.64 1.81E-01 0.80 217207_s_at BTNL3 butyrophilin-like 3 10917 1.46E-03 0.74 7.77E-01 0.96 1561589_a_ at NBEAL1 neurobeachin-like 1 65065 1.50E-03 0.76 6.38E-01 1.05 Peptidylprolyl isomerase domain and WD repeat 236999_at PPWD1 containing 1 23398 1.81E-03 0.57 6.69E-01 0.90 232410_at RCOR3 REST corepressor 3 55758 1.88E-03 0.75 6.48E-01 0.94 zyg-11 homolog B (C. 202456_s_at ZYG11BL elegans)-like 10444 1.90E-03 0.60 9.85E-01 1.01 DEAD (Asp-Glu-Ala-Asp) box 1558120_at DDX3X polypeptide 3, X-linked 1654 1.94E-03 0.57 7.63E-01 0.96 gb:AF119896.1 /DB_XREF=gi:7770228 /FEA=FLmRNA /CNT=3 /TID=Hs.283978.0 /TIER=FL /STK=0 /UG=Hs.283978 /DEF=Homo sapiens PRO2751 mRNA, complete cds.
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