Supplementary Tables Table name Supplementary Table 4.1 Regression associations between LKB1 loss signature and inhibitors in GDSC study Supplementary Table 4.2 Regression associations between LKB1 loss signature and inhibitors in CTRP study Supplementary Table 4.3 Regression associations between LKB1 loss signature and inhibitors in CCLE study Supplementary Table 4.1 Regression associations between LKB1 loss signature and inhibitors in GDSC study Linear regression parameters GDSC Study compound Reported target Observations Estimate (IC50 log2) Std. Error t-value P-Value Trametinib MAP2K1 (MEK1), MAP2K2 (MEK2) 755 -1.65 0.2 -8.08 2.67E-15 17-AAG HSP90 717 -1.18 0.15 -7.66 5.98E-14 RDEA119 (rescreen) MAP2K1 (MEK1), MAP2K2 (MEK2) 745 -1.06 0.14 -7.38 4.40E-13 PD-0325901 MAP2K1 (MEK1), MAP2K2 (MEK2) 708 -1.12 0.15 -7.27 9.61E-13 RDEA119 MAP2K1 (MEK1), MAP2K2 (MEK2) 707 -1.09 0.16 -6.94 8.98E-12 CI-1040 MAP2K1 (MEK1), MAP2K2 (MEK2) 709 -0.53 0.13 -4.09 4.71E-05 BMS-754807 IGF1R 756 -0.5 0.14 -3.44 0.00062 rTRAIL TR10A (DR4), TR10B (DR5) 778 -0.38 0.12 -3.3 0.001 FH535 unknown 757 -0.28 0.1 -2.71 0.0068 OSI-906 IGF1R 756 -0.32 0.13 -2.56 0.011 Afatinib (rescreen) ERBB2, EGFR 773 -0.34 0.13 -2.54 0.011 VX-11e ERK 787 -0.3 0.12 -2.48 0.013 Afatinib ERBB2, EGFR 715 -0.28 0.12 -2.35 0.019 AZD6244 MAP2K1 (MEK1), MAP2K2 (MEK2) 808 -0.3 0.14 -2.22 0.027 Cetuximab EGFR 738 -0.17 0.08 -2.02 0.043 BMS-536924 IGF1R 815 -0.22 0.12 -1.92 0.055 Bryostatin 1 PRKC 756 -0.14 0.07 -1.83 0.067 Erlotinib EGFR 332 -0.32 0.18 -1.76 0.079 Docetaxel Microtubules 716 -0.22 0.13 -1.71 0.088 Epothilone B Microtubules 760 -0.24 0.16 -1.51 0.13 Lapatinib ERBB2, EGFR 358 -0.23 0.17 -1.4 0.16 AZ628 BRAF 364 -0.37 0.28 -1.36 0.18 Mitomycin C DNA crosslinker 761 -0.15 0.13 -1.11 0.27 GW 441756 NTRK1 715 -0.1 0.09 -1.11 0.27 AKT inhibitor VIII AKT1, AKT2, AKT3 767 -0.05 0.09 -0.64 0.52 Bleomycin DNA damage 753 -0.13 0.2 -0.63 0.53 XAV 939 TNKS1 (tankyrase-1) 777 -0.04 0.07 -0.56 0.58 Thapsigargin sarco-endoplasmic reticulum Ca2+-ATPases 747 -0.1 0.17 -0.55 0.58 NVP-TAE684 ALK 370 -0.07 0.23 -0.3 0.76 QS11 ARFGAP 760 -0.03 0.12 -0.22 0.83 SB590885 BRAF 699 -0.02 0.1 -0.18 0.86 HG-5-88-01 EGFR, ADCK4 400 -0.01 0.14 -0.06 0.95 CP724714 ERBB2 787 0 0.08 -0.01 1 Bexarotene Retinioic acid X family agonist 751 0 0.09 0.04 0.97 GSK-650394 SGK3 751 0.02 0.14 0.11 0.91 AS601245 JNK 757 0.03 0.1 0.29 0.77 Gefitinib EGFR 712 0.03 0.09 0.3 0.76 LY317615 PRKCB (PKCbeta) 784 0.05 0.14 0.32 0.75 Embelin XIAP 761 0.03 0.09 0.32 0.75 Dabrafenib BRAF 736 0.06 0.17 0.36 0.72 Cytarabine DNA synthesis 712 0.05 0.14 0.36 0.72 Doxorubicin DNA intercalating 760 0.05 0.14 0.36 0.72 BIRB 0796 p38, JNK2 707 0.04 0.08 0.48 0.63 Vinorelbine Microtubules 770 0.07 0.14 0.49 0.62 CCT007093 PPM1D 781 0.03 0.06 0.53 0.6 Bleomycin (50 uM) DNA damage 793 0.12 0.17 0.68 0.5 JQ12 HDAC 766 0.11 0.14 0.77 0.44 Tipifarnib Farnesyl-transferase (FNTA) 759 0.11 0.14 0.82 0.41 GSK-1904529A IGF1R 760 0.05 0.06 0.83 0.41 Gemcitabine DNA replication 755 0.2 0.23 0.87 0.38 JNK-9L JNK 769 0.08 0.09 0.91 0.36 PF-4708671 RPS6KB1 (p70S6KA) 772 0.08 0.08 1.03 0.3 GDC0941 (rescreen) PI3K 752 0.12 0.11 1.11 0.27 AZD-0530 SRC, ABL1 371 0.2 0.17 1.16 0.25 Elesclomol HSP70 717 0.19 0.16 1.16 0.25 CCT018159 HSP90 764 0.11 0.09 1.18 0.24 KIN001-055 JAK3, MNK1 787 0.11 0.09 1.22 0.22 PLX4720 BRAF 715 0.14 0.12 1.23 0.22 PLX4720 (rescreen) BRAF 776 0.13 0.1 1.3 0.19 AUY922 HSP90 753 0.18 0.14 1.36 0.18 Supplementary Table 4.1 Regression associations between LKB1 loss signature and inhibitors in GDSC study RO-3306 CDK1 717 0.12 0.09 1.37 0.17 SB 216763 GSK3A, GSK3B 645 0.12 0.09 1.39 0.16 JW-7-52-1 MTOR 352 0.39 0.28 1.39 0.16 Pyrimethamine Dihydrofolate reductase (DHFR) 363 0.33 0.22 1.49 0.14 Dasatinib ABL, SRC, KIT, PDGFR 362 0.53 0.36 1.5 0.14 HG-5-113-01 LOK, LTK, TRCB, ABL(T315I) 400 0.16 0.11 1.5 0.13 TGX221 PI3Kbeta 362 0.26 0.17 1.51 0.13 PHA-665752 MET 371 0.21 0.14 1.54 0.12 MK-2206 AKT1, AKT2 693 0.2 0.13 1.6 0.11 Sorafenib PDGFRA, PDGFRB, KDR, KIT, FLT3 365 0.32 0.2 1.62 0.11 A-770041 SRC family 365 0.43 0.26 1.69 0.092 EHT 1864 Rac GTPases 784 0.13 0.08 1.7 0.09 Bortezomib Proteasome 362 0.41 0.23 1.74 0.082 AS605240 PI3Kgamma 782 0.25 0.14 1.75 0.08 TW 37 BCL2, BCL2L1 781 0.18 0.1 1.78 0.075 MG-132 Proteasome 363 0.39 0.22 1.8 0.073 BMN-673 PARP1 774 0.29 0.16 1.8 0.072 (5Z)-7-Oxozeaenol MAP3K7 (TAK1) 775 0.22 0.12 1.83 0.067 MLN4924 NEDD8-activating enzyme 610 0.28 0.15 1.84 0.066 AMG-706 VEGFR, RET, c-KIT, PDGFR 717 0.15 0.08 1.89 0.06 WH-4-023 SRC family, ABL 362 0.6 0.31 1.93 0.055 BMS-509744 ITK 365 0.3 0.16 1.94 0.053 Paclitaxel Microtubules 365 0.54 0.28 1.94 0.053 PF-562271 FAK 754 0.18 0.09 2.01 0.044 Bicalutamide ANDR (androgen receptor) 823 0.15 0.07 2.09 0.037 A-443654 AKT1, AKT2, AKT3 364 0.43 0.2 2.11 0.035 Roscovitine CDKs 358 0.31 0.15 2.13 0.034 GDC0941 PI3K (class 1) 708 0.29 0.13 2.15 0.032 WZ-1-84 BMX 364 0.33 0.15 2.16 0.031 PD-0332991 CDK4, CDK6 693 0.32 0.14 2.23 0.026 GW843682X PLK1 365 0.59 0.26 2.24 0.026 FR-180204 ERK 787 0.17 0.07 2.28 0.023 NSC-87877 PTPN6 (SHP-1), PTPN11 (SHP-2) 766 0.17 0.07 2.29 0.022 XMD11-85h BRSK2, FLT4, MARK4, PRKCD, RET, SPRK1 399 0.23 0.1 2.29 0.022 S-Trityl-L-cysteine KIF11 363 0.52 0.22 2.33 0.02 YK 4-279 RNA helicase A 676 0.28 0.12 2.36 0.019 KIN001-135 IKKE 364 0.22 0.09 2.36 0.019 BI-2536 PLK1, PLK2, PLK3 364 0.55 0.23 2.37 0.019 JNK Inhibitor VIII JNK 715 0.16 0.07 2.38 0.018 MS-275 HDAC 362 0.54 0.22 2.42 0.016 OSU-03012 PDPK1 (PDK1) 759 0.26 0.11 2.43 0.015 Phenformin AAPK1 (AMPK) agonist 779 0.39 0.16 2.48 0.013 Salubrinal GADD34-PP1C 360 0.4 0.16 2.53 0.012 Obatoclax Mesylate BCL2, BCL2L1, MCL1 754 0.37 0.15 2.54 0.011 MP470 PDGFR 782 0.33 0.13 2.54 0.011 NU-7441 PRKDC (DNAPK) 713 0.21 0.08 2.6 0.0096 Nutlin-3a MDM2 717 0.31 0.12 2.61 0.0093 VX-680 AURKA, AURKB, AURKC, FLT3, ABL1, JAK2 359 0.77 0.29 2.66 0.0081 FTI-277 Farnesyl transferase (FNTA) 769 0.17 0.06 2.71 0.0069 CEP-701 FLT3, JAK2, NTRK1, RET 715 0.36 0.13 2.75 0.0062 AG-014699 PARP1, PARP2 782 0.23 0.08 2.75 0.006 Midostaurin KIT 770 0.3 0.11 2.78 0.0055 DMOG Prolyl-4-Hydroxylase 767 0.34 0.12 2.8 0.0053 Bosutinib SRC, ABL, TEC 717 0.33 0.12 2.84 0.0047 CGP-60474 CDK1,CDK2,CDK5,CDK7,CDK9 364 0.52 0.18 2.87 0.0044 QL-VIII-58 MTOR, ATR 401 0.42 0.15 2.87 0.0043 Etoposide TOP2 770 0.48 0.17 2.87 0.0042 MPS-1-IN-1 MPS1 785 0.33 0.12 2.88 0.0041 SB52334 ALK5 786 0.31 0.11 2.9 0.0038 BAY 61-3606 SYK 757 0.37 0.13 2.91 0.0037 Cisplatin DNA crosslinker 716 0.31 0.1 2.95 0.0033 EKB-569 EGFR 786 0.42 0.14 2.96 0.0032 Supplementary Table 4.1 Regression associations between LKB1 loss signature and inhibitors in GDSC study JQ1 BRD4 828 0.39 0.13 2.98 0.0029 GNF-2 ABL [T315I] 362 0.38 0.13 2.99 0.0029 Sunitinib PDGFRA, PDGFRB, KDR, KIT, FLT3 364 0.74 0.24 3.03 0.0027 Pazopanib VEGFR, PDGFRA, PDGFRB, KIT 757 0.35 0.11 3.11 0.002 Parthenolide NFKB1 364 0.56 0.18 3.19 0.0015 Imatinib ABL, KIT, PDGFR 371 0.49 0.15 3.2 0.0015 JNJ-26854165 MDM2 779 0.27 0.08 3.21 0.0014 ZM-447439 AURKB 685 0.38 0.12 3.23 0.0013 AZD7762 CHEK1, CHEK2 716 0.43 0.13 3.23 0.0013 LAQ824 HDAC 761 0.33 0.1 3.27 0.0011 Crizotinib MET, ALK 370 0.55 0.17 3.27 0.0012 ABT-888 PARP1, PARP2 716 0.21 0.06 3.29 0.001 LFM-A13 BTK 759 0.21 0.06 3.31 0.00097 PAC-1 CASP3 agonist 750 0.35 0.11 3.32 0.00095 KU-55933 ATM 715 0.29 0.09 3.34 0.0009 Rapamycin MTOR 332 1.03 0.31 3.34 0.00093 NVP-BHG712 EPHB4 787 0.47 0.14 3.35 0.00084 KIN001-266 MAP3K8 (COT) 787 0.33 0.09 3.51 0.00047 GW-2580 CSF1R (cFMS) 787 0.21 0.06 3.56 0.0004 ATRA Retinoic acid and retinoid X receptor agonist 707 0.41 0.12 3.57 0.00038 YM155 BIRC5 (Survivin) 762 0.75 0.2 3.66 0.00027 XMD8-92 MAP2K5 (ERK5) 400 0.42 0.11 3.75 0.0002 IOX2 EGLN1 787 0.23 0.06 3.8 0.00015 THZ-2-49 CDK9 785 0.73 0.19 3.83 0.00014 CMK RSK 364 0.67 0.17 3.84 0.00015 NVP-BEZ235 PI3K (Class 1) and MTORC1/2 709 0.41 0.11 3.84 0.00013 YM201636 FYV1 787 0.41 0.11 3.87 0.00012 ABT-869 VEGFR and PDGFR family 787 0.33 0.08 3.92 9.60E-05 Olaparib PARP1, PARP2 807 0.34 0.09 3.95 8.67E-05 FMK RSK 702 0.28 0.07 3.95 8.44E-05 5-Fluorouracil DNA antimetabolite 783 0.59 0.15 3.96 8.15E-05 XL-880 MET 784 0.47 0.12 3.97 7.86E-05 Z-LLNle-CHO g-secretase 364 0.72 0.18 3.98 8.32E-05 XMD8-85 MAP2K5 (ERK5) 359 0.68 0.17 4 7.71E-05 CGP-082996 CDK4 364 0.65 0.16 4.12 4.64E-05 KIN001-102 AKT1 785 0.53 0.13 4.14 3.92E-05 BMS-345541 IKBKB 786 0.42 0.1 4.16 3.58E-05 Axitinib PDGFR, KIT, VEGFR 715 0.49 0.12 4.19 3.13E-05 Shikonin unknown 767 0.47 0.11 4.2 3.02E-05 BMS-708163 g-secretase 830 0.27 0.06 4.2 2.94E-05 PFI-1 BRD2, BRD3, BRD4 790 0.38 0.09 4.2 2.92E-05 QL-XII-61 BTK 378 0.58 0.14 4.22 3.03E-05 SNX-2112 HSP90 780 0.77 0.18 4.24 2.49E-05 AZD8055 MTORC1/2 709 0.42 0.1 4.28 2.14E-05 Nilotinib ABL 687 0.54 0.13 4.31 1.89E-05 CHIR-99021 GSK3B 828 0.36 0.08 4.31 1.82E-05 Vinblastine Microtubules 716 0.56 0.13 4.31 1.85E-05 SL 0101-1 RSK, AURKB, PIM3 706 0.28 0.07 4.31 1.85E-05 SGC0946 Q8TEK3 (DOT1L) 768 0.21 0.05 4.35 1.53E-05 GSK269962A ROCK1, ROCK2 818 0.52 0.12 4.37 1.40E-05 Lenalidomide TNFA 717 0.31 0.07 4.44 1.05E-05 AC220 FLT3 786 0.41 0.09 4.49 8.29E-06 VX-702 p38 713 0.34 0.07 4.58 5.54E-06 Cyclopamine SMO 358 0.64 0.14 4.66 4.55E-06 piperlongumine Increases ROS levels 786 0.37 0.08 4.68 3.43E-06 Camptothecin TOP1 715 0.72 0.15 4.68 3.43E-06 CH5424802 ALK 784 0.44 0.09 4.72 2.79E-06 PXD101, Belinostat #N/A 765 0.76 0.16 4.73 2.66E-06 BX-795 TBK1, PDPK1, IKK, AURKB, AURKC 716 0.53 0.11 4.74 2.58E-06 AT-7519 CDK9 783 0.8 0.17 4.79 1.97E-06 TAK-715 p38a 787 0.47 0.1 4.8 1.90E-06 AZD6482 PI3Kbeta 826 0.52 0.11 4.8 1.87E-06