Supplementary Figure 1.Lepikhova etal.
Sepantronium bromide
Methylprednisolone 2−methoxyestradiol Cyclophosphamide S−tr Aminoglutethimide Megestrol acetate AZD1152−HQ Dexamethasone Mercaptopurine
ityl−L−cysteine Galiellalactone Uracil mustard Temozolomide Bendamustine Geldanamycin PF−04708671 PF−04691502 NVP−RAF265 Doramapimod Camptotechin Ruboxistaurin BMS−754807 Ridaforolimus
Lenalidomide Dauno Procarbazine Omacetaxine Cabozantinib Prednisolone Capecitabine Temsirolimus Methotrexate Chlorambucil
Cyclopamine Mit Bicalutamide VER 155008 Mocetinostat Hydroxyurea Dacarbazine Gemcitabine Lasofoxifene Tacedinaline Streptozocin Vemurafenib Exemestane Thioguanine Mitomycin C
Thalidomide Regorafenib Sotrastaurin Pipobroman Galunisertib Bimatoprost Re Enzastaurin Bryostatin 1 Bryostatin Fludarabine Anastrozole D Vismodegib Selumetinib Fluorouracil Lestaurtinib
Abiraterone
Carmustine
Ixabepilone Carboplatin Bexarotene Clofarabine Prednisone Altretamine Thio−TEPA
Saracatinib Vandetanib Carfilzomib Pilocarpine Finasteride Pentostatin SB 743921 Fulvestrant Everolimus Toremifene Fingolimod Binimetinib Tarenflurbil Floxuridine Vinblastine Danusertib Rabusertib Gandotinib Azacitidine Tosedostat Nelarabine Quizartinib Anagrelide Nintedanib Amonafide T Plicamycin Pimase Tacrolimus Palbociclib Decitabine Nilutamide Patupilone Allopurinol Pazopanib Omipalisib Raloxifene Vincristine PF477736 Motesanib Ruxolitinib Imiquimod T Lomustine Cane Bleomycin T Navitoclax Rucaparib Ifosfamide Tandutinib o Cladribine Obatoclax AZD 7762 Tamoxifen Etoposide Entinostat Sonidegib
o Docetaxel Tofacitinib Volasertib I Buparlisib
Flutamide Celecoxib Ida V Dactolisib MK−0752 APR−246 MK−2206 SNS−032 eniposide Goserelin Tamatinib Cediranib Tivantinib Tivozanib Sorafenib AZD1480 AZD4547 AZD8055 AZD1775 Paclitaxel Plerixafor ABT−751 XA Dasatinib Crizotinib KX2−391 r Ponatinib opotecan Tipifarnib r Sirolimus Vatalanib Letrozole PF−3845 T T
Lapatinib Sonolisib f xo Apitolisib Tepotinib Alvocidib OSI−027 Masitinib xantrone Seliciclib Idelalisib Linsitinib Busulfan UCN−01 Foretinib Sunitinib Mitotane Cisplatin Veliparib Dovitinib Olaparib inotecan
ametinib ametinib Tretinoin al Indibulin Nutlin−3 Linifanib Gefitinib E Pictilisib Brivanib Alisertib AK−733 AK−901
Nilotinib BI 2536 AT9283 A Iniparib Axitinib Fasudil AT 101 (−)JQ1 (+)JQ1 r r r r r V−939 f lotinib ubicin ubicin ubicin ubicin atinib r tinib r PA tib
CELL LINES
DRUGS Supplementary Figure 1. Response of selected compounds showing activity to 45 UT-SCC cell lines. Heat map of drug response across the cell lines. The used drugs are shown on the Y-axis and cell lines on the X-axis. The cell lines are clustered based on the differential DSS. Different clusters are marked with Roman numerals. The biggest drug classes are highlighted in the figure. Ser/Thr Non−RTK/multi MEK RTK mTOR PI3K/mTOR PI3K CDK kinase target kinase B inhibitors inhibitors inhibitors inhibiors inhibitors inhibitors inhibitors inhibitors
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BI 2536 Afatinib TAK−733 Alisertib UCN−01 ErlotinibGefitinib AZD8055 OSI−027 IdelalisibPictilisib KX2−391 SNS−032 Volasertib LapatinibLinsitinib Sirolimus ApitolisibDactolisib Buparlisib Sonolisib Dasatinib Alvocidib BinimetinibPimasertib Trametinib Canertinib Everolimus Omipalisib Danusertib Saracatinib RefametinibSelumetinib BMS−754807 Midostaurin RidaforolimusTemsirolimus PF−04691502 Drug name Apoptosis Platinum Mitotic Antitumor HDAC HSP90 Antimetabolites inducing Others agents inhibitors antibiotics inhibitors inhibitors drugs
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AT 101 BIIB021 Cisplatin ABT−751 IndibulinPaclitaxel Docetaxel PatupiloneVincristine ObatoclaxSB 743921BelinostatEntinostat Vorinostat Carboplatin Vinblastine Plicamycin EnzastaurinQuisinostat Luminespib Carfilzomib FluorouracilGemcitabineMethotrexateThioguanine MocetinostatTacedinaline Omacetaxine Dactinomycin AlvespimycinGeldanamycinTanespimycin Mercaptopurine Drug name Sepantronium bromide Supplementary Figure 2. Lepikhova et al. Supplementary Figure 2. Grouping of the used drugs based on their functional categories.
Boxplots are drawn with R language ggplot2 system function geom_boxplot. The upper and lower edges of the box are the first and third quartiles of the response. Median response is shown by horizontal line in each box. Whiskers extend to 1.5 times the inter-quartile range, which is the distance between the box edges. Values beyond the box edges are marked as outliers with a plus sign. A Scr ctrl afatinib B RAB25 siRNA afatinib IC50 IC50
100 DSS 13.1 100 DSS 9.8
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% inhibition 0 % inhibition 0
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Scr ctrl erlotinib RAB25 siRNA erlotinib C IC50 D IC50
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0.1 10 100 1000 10000 0.1 10 100 1000 10000 conc (nM) conc (nM) E F Scr ctrl afatinib FAM83H siRNA afatinib IC50 IC50
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G Scr ctrl erlotinib H FAM83H siRNA erlotinib IC50 IC50
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I Scr SiRNA Scr SiRNA RAB25 FAM83H
alpha- alpha- tubulin tubulin UT_SCC_8 UT_SCC_14
Supplementary Figure 3. Lepikhova et al. Supplementary Figure 3. Transient knock-down of RAB25 and FAM83H impairs the cellular response to EGFR inhibitors afatinib and erlotinib. Drug response curves for A-B, afatinib and C-D, erlotinib in control and RAB25 siRNA treated UT-SCC-8 cells, respectively. Drug response curves for E-F, afatinib and G-H, erlotinib in control and FAM83H siRNA treated UT-SCC-14 cells, respectively. The vertical grey line shows the IC50 value. The triplicate % inhibition values for each concentration are shown as grey dots. I, Western blots show efficacy of the RAB25 and FAM83H silencing by siRNAs.