PDF file - 48K, RPPA data for the colon and melanoma cell lines. Values are log-base 2, normalized to both total protein loading per sample and the median protein expression. HT29/WiDr, and Colo201/Colo205 are derived from the same patient under different time courses/conditions, and therefore may be provide limited additional data (Semple TU et al., Cancer Res. 1978 May;38(5):1345-55, Chen TR et al Cancer Genet Cytogenet. 1987 Jul;27(1):125-34). Sensitivity analysis demonstrates no change in the conclusions with the inclusion or exclusion of these isogenic cell lines.

Supplemental Figure Legends; Supplemental Table Legends

PDF file - 84K, HT29 and Colo205 parental and PLX-resistant (RC) cell lines subjected to FISH for EGFR. A) Representative fields from each of the 4 cell lines are shown below, with red EGFR probe and green Chr7 centromeric probe. B) FISH scoring confirms HT29RC amplification, compared to centromeric control.

Supplementary Table 1, Figures 1-3 from β-Lapachone Micellar Nanotherapeutics for Non–Small Cell Lung Cancer Therapy

PDF file - 124 KB, Synthesis of Cromolyn Analogs:Lead compound C5OH synthesis is presented in material and method sections. Other analogs synthesis procedure is provided as supplementary material.

Supplemental Figure 1. Elevated NQO1 expression in patients with HNC correlates with poor overall survival to standard therapy; Supplemental Figure 2. Functional shRNA-NQO1 knockdown rescues β-lapinduced cell death; Supplemental Figure 3. β-Lap-induced NQO1 dependent DNA damage and NAD+ depletion; Supplemental Figure 4. Combination sublethal doses of β-lap and low dose IR induce NQO1 dependent anti-cancer lethality; Supplemental Figure 5. Cooperative antitumor efficacy using a combination of IR and β-lap to treat HNC xenograft models; Figure 6. Expression of Ki-67 after combination of β-lap and IR in HNC xenograft models; Supplemental Table 1. NQO1 enzyme activity and abrogation of activity in 41 HNC cell lines and primary human IMR90 fibroblasts; Supplemental Table 2. Equitoxic doses comparing single to combined treatment in HNC cells; Supplemental Table 3. Individual patient gender, age, subsite, stage, histology and IHC scoring for NQO1 and Catalase

PDF file - 36K, Correlation of EGFR and PTEN expression by RPPA and sensitivity to PLX4720. There is no statistically significant correlation between the EGFR expression level and sensitivity to PLX4720 (P=0.10, Spearman rank), although this is influenced by outliers at both extremes of sensitivity. PTEN expression is likewise not statistically significantly correlated with sensitivity (P=0.4). Together, either loss of PTEN or higher EGFR expression is associated with resistance to PLX4720 (P=0.048, Fisher's exact).

PDF file - 46K, HT29 and Colo205 parental and PLX-resistant (RC) cell lines were profiled by Affymetrix U133A for gene expression. Additional candidate genes in the MAPK and AKT pathway are shown below. Each point represents the relative expression of a single probe (relative expression of resistant cell to parental) for each of the specified genes.

Supplementary Figure 3 from Deubiquitinase Inhibition by Small-Molecule WP1130 Triggers Aggresome Formation and Tumor Cell Apoptosis

PDF file - 38K, KRAS, BRAF, PIK3CA, and PTEN status of utilized CRC cell lines.The mutation data was obtained from the Sanger Institute Catalogue Of Somatic Mutations In Cancer web site, http://www.sanger.ac.uk/cosmic. Bamford et al (2004) The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website. Br J Cancer, 91,355-358.

PDF file - 44K, The combination therapy with PLX4720 and azacytidine was repeated in HT29 cells first treated with siRNA to PTEN . Silencing PTEN was not sufficient to fully abolish the synergy seen with the combination (* P<0.05).

PDF file - 30K, BRAF mutant cell lines utilized in the RPPA analysis. Cells were lysed at approximately 70% confluence in 10% serum. Of note, Colo201 and Colo205 are derived from the same colon cancer patient, as are HT29 and WiDr. Cell lines were obtained from the American Type Culture Collection, or the Ludwig Institute of Cancer Research. Cell line identities were confirmed by STR testing, and were verified to be Mycoplasma-free. All lines were grown in DMEM/F-12, or RPMI1640 medium supplemented with 10% FBS and 2 mmol/L glutamine or MEM, (10S, sodium pyruvate, L-glutamine, vitamins, and nonessential amino acids). Cells were incubated in 5% CO2 at 37{degree sign}C.

PDF file - 338K, Cells were incubated for 24h (HT29, Colon205) or 48 h (RKO) with PLX4720 (1 M for all cell lines), LY294002 (15 M for all cell lines) or their combination. Cells were then harvested and stained with propidium iodide. DNA concentrations were measured by FACS. The data represent mean values from three independent experiments. (# represents P < 0.01)

PDF - 495K, Supplementary Table 1: Gene Alterations in AML Cell Lines used in This Study Supplementary table 52:Gene alterations and cytogenetic information on 10 periphoral blood or bone marrow samples obtained from AML patients Fig. S1. Molecular structures of drugs used in this study. Fig. S2. The Chou-Talalay method Chou et al. Cancer Res. 2010; 70: 440-446 was used to determine combination indices (CIs) in AML cell lines treated with combination of AZD8055 and selumetinib for 48 hours. Fig. S3. OCI/AML3 cells were pretreated with proteasome inhibitors bortezemib (0.01 micromol/L) or MG132 (0.5 micromol/L) for 2 hours following by combination of AZD8055 (0.4 micromol/L) and selumetinib (0.2 micromol/L) for additional 48 hours. The apoptosis induction was measured using flow cytometry. Fig. S4. U937 cells were electroporated with Bim siRNA or scrambled siRNA for 24 hours, treated with AZD8055 (0.4 micromol/L) and/or selumetinib (0.2 micromol/L) for 48 hours, and examined for apoptosis induction. Inset: knockdown of basal level of Bim protein expression. Fig. S5. AML cells were treated with indicated doses of selumetinib for 48 hours and apoptosis induction was determined using flow cytometry by measuring percentage of Annexin V positivity. Fig. S6. AML cells were treated with indicated doses of AZD8055 for 48 hours and apoptosis induction was determined using flow cytometry by measuring percentage of Annexin V positivity. Fig. S7. OCI/AMl3_shGFP and OCI/AMl3_shMcl-1 AML cells were treated with indicated doses of ABT-737 for 48 hours and apoptosis induction was determined using flow cytometry by measuring Annexin Vneg/PIneg population.

PDF file - 140K, HT29 and Colo205 parental and PLX-resistant (RC) cell lines were profiled by Affymetrix MIP array (OncoScan FFPE Express 2.0 Services) for copy number. The following copy number plots were produced by Affymetrix Nexus CN 6.0. (build 6461). In the HT29 parental and HT29RC, the black arrows represent an increase in copy number in chromosome 7p acquired in the HT29RC. Similarly, in the Colo205RC, there is an acquired increase in copy number in chromosome 12p, denoted by the black arrow.

Supplementary Figure 4 from Deubiquitinase Inhibition by Small-Molecule WP1130 Triggers Aggresome Formation and Tumor Cell Apoptosis

PDF file, 1661K, Supplemental Figure S1- Chemical Structures. Supplemental Figure S2-Oxygen Consumption in MCF-7 Cells treated with or without betalapchone and dicoumarol. Supplemental Figure S2 legend. Supplemental Figure S3-Survival assay for normal mammary epithelial cells treated with betalapachone with or without dicoumarol. Supplemental Figure S3 legend. Supplemental Figure S4-Survival assay for MDA-MB231 cells treated with or without quinones and ROS scavengers. Supplemental Figure S4 legend. Supplemental Figure S5-Westernblot of MCF-7 cells treated with betalapachone with or without catalase. Supplemental Figure S5 legend. Supplemental Figure S6-Proteolysis of PARP in MCF-7 cells treated with betalapachone or staurosporine. Supplemental Figure S6 legend. Supplemental Figure S7- NQO1 mediated futile cycle of betalapachone. Supplemental Figure S7 legend. Supplemental Figure S8- Western blot and analysis of NQO1 to Catalase ratios in Breast Cancer Cell lines. Supplemental Table 1- NQO1 enzymatic activity in breast cancer cell lines. Supplemental Table 1 legend.

Supplementary Table 1 from Mechanisms of Antileukemic Activity of the Novel Bcl-2 Homology Domain-3 Mimetic GX15-070 (Obatoclax)

Supplementary Table 1 from STAT3 Mediates Resistance to MEK Inhibitor through MicroRNA miR-17

Supplementary Figure 1 from Pyridone 6, A Pan-Janus–Activated Kinase Inhibitor, Induces Growth Inhibition of Multiple Myeloma Cells