High-throughput drug screen (HTDS) reveals ARS1620 and PI3K pathway inhibitors synergies and a heterogeneous pattern of RTK synergies. High-throughput.

Slides:

Advertisements

Similar presentations

Figure 5 Mutational heterogeneity in oesophageal and gastric cancer

Advertisements

Modulation of KRASG12C activity alters ARS-853 target engagement and supports novel therapeutic strategies for targeting KRAS. A, schematic for altering.

Figure 4 Possible combination therapies CDK4/6 inhibitors

Figure 2 Therapeutic targeting of the PI3K/AKT/mTOR pathway

High-throughput analysis of informative CpG sites for the four studied tumor suppressor genes (A-D). High-throughput analysis of informative CpG sites.

AKT dependence of ovarian cancer cell lines.

ASSIGNMENT 10 Use the UP and DOWN tags as provided and query the LINCS. These are the KRAS-DEP (UP) and KRAS-IND (DOWN) gene signatures from Singh et al.

IL32 prompts cell activation and cancer-related pathways.

High-throughput combination drug screening to nominate potent drug combinations. High-throughput combination drug screening to nominate potent drug combinations.

Genetic landscape of salivary duct carcinoma.

K-Means clustering of protein and mRNA expression patterns after PPAR agonists treatments. k-Means clustering of protein and mRNA expression patterns after.

A genome-wide RNAi pooled screen identifies NF1 as a key determinant of RAF inhibitor sensitivity in melanoma cells. A genome-wide RNAi pooled screen identifies.

Reproducibility of DeathPro drug screens

Predicting drug sensitivity from proteomic (RPPA) data clusters.

CD16 uses additional pathways for killing.

NAPRT expression correlates to sensitivity for NAMPT inhibitors and to methylation of the CpG island of the NAPRT promoter. NAPRT expression correlates.

Derivation of ImSig. Derivation of ImSig. A, An example of a correlation network generated from a tissue data set where nodes represent unique genes and.

Sensitivity analysis of cellular responses to perturbation of the DNA damage response signaling in the presence of chemotherapies. Sensitivity analysis.

Table A and B, in vitro synergy of romidepsin and pralatrexate (PDX) in TCL cell lines. Table A and B, in vitro synergy of romidepsin and pralatrexate.

SiRNA screening identifies genes required for the viability of Pim1-ovexpressing prostate cells. siRNA screening identifies genes required for the viability.

Evaluation of top candidate clones for selective killing in bispecific antibody format. Evaluation of top candidate clones for selective killing in bispecific.

Dietary plant extracts inhibit NF-κB activation in vitro.

A, Top inhibitors of Ba/F3 transformed with CD74–ROS1, color coded by clinical development status: FDA-approved (green), phase III (yellow), phase II (blue),

Frequent alterations identified and potential actionability.

Protein expression profile in a dasatinib-resistant cell line.

Matriptase-2 inhibited breast tumor development in vivo.

FGFR3 mutation analysis of a selection of urine samples from patients included with an FGFR3-mutant (MT) tumor. FGFR3 mutation analysis of a selection.

A, iDC (top) or mDC (bottom) were loaded with or without 10 pfu/cell reovirus, and cultured with Mel-888 cells in the presence of blocking serum. A, iDC.

A, one-step viral growth curves: RT treatment increased the virus yield in MV-CEA–treated U87 cells by up to 2 log as compared with MV-CEA infection only.

MiR-200c is a PI3K–AKT signaling pathway regulator in CRC

Peptide dose-response curves were done to estimate the avidity of these HTL for peptide TARP1-14 (A) and TARP14-27 (B-E) using autologous PBMCs and dendritic.

Effect of GSK3β inhibition on cell survival and proliferation of glioblastoma cells. Effect of GSK3β inhibition on cell survival and proliferation of glioblastoma.

Cells lacking CDK6 kinase function are required to mutate p53.

Dysregulated NF-κB activation in Il1r8+/+/lpr and Il1r8−/−/lpr mice.

Replication stress inhibition synergizes with DNA damaging agents in human cells. Replication stress inhibition synergizes with DNA damaging agents in.

Simplified BRAF signaling network.

Nested RT-PCR of Mammaglobin and CK19 mRNA in plasma and circulating cells of controls (C) and patients (T) with breast cancer. Nested RT-PCR of Mammaglobin.

ABT-100 inhibits PI3K activity and p85 tyrosine phosphorylation.

A, Stacked Venn plots of the significantly associated (FDR < 25%) KEGG pathways for 3 imaging subtypes with GSEA. B, Pathway activity scores for 3 imaging.

IGF-I partially protects Rh30 cells from apoptosis despite simultaneous inhibition of PI3K-Akt and MAP kinase pathways. IGF-I partially protects Rh30 cells.

Characterization of DNA-PK and PARP-1 levels and activities in the cell lines studied. Characterization of DNA-PK and PARP-1 levels and activities in the.

Tivantinib behaves as an antimitotic agent.

Increased apoptotic levels after combined treatment with vincristine (VCR) and imatinib. Increased apoptotic levels after combined treatment with vincristine.

Increased apoptotic levels after combined treatment with DXR and imatinib. Increased apoptotic levels after combined treatment with DXR and imatinib. A–D.

MAPK/ERK signaling regulates TLR4 gene expression in response to BRAFV600E. MAPK/ERK signaling regulates TLR4 gene expression in response to BRAFV600E.

Quantitative PTEN protein expression is associated with pertuzumab sensitivity in vitro and trastuzumab resistance in vivo. Quantitative PTEN protein expression.

Efficacy summary for patients with gastric/GEJ adenocarcinoma (part B)

Combined inhibition of coamplified RTKs is required for response.

Enhanced expression of Cap43 gene by nickel in breast cancer cell lines. Enhanced expression of Cap43 gene by nickel in breast cancer cell lines. Expression.

Histology (H&E; original magnification, ×100 for B-2P/C-12P/C-64P and ×40 for C-10P; top) of small-sized lung adenocarcinomas and immunohistochemical staining.

Top, NEPC biology is estimated to drive approximately 25% of the lethal prostate cancers indicated by the blue zone. Top, NEPC biology is estimated to.

Global mutational landscape of the 170 lung adenocarcinoma patients (discovery cohort). Global mutational landscape of the 170 lung adenocarcinoma patients.

The best response for target lesions per patient for patients with target lesions assessed at baseline and at least 1 follow-up. The best response for.

The effects of AZD1775 and olaparib on DNA damage response signaling.

No single ALK mutations confer high-level resistance to lorlatinib.

Cell lines from hematologic cancers, including multiple myeloma (MM), AML, and DLBCL, exhibit a strong dependency on MCL1 for survival. Cell lines from.

Interaction of NHEJ and HR pathways in PCO cultures.

Establishment of HeLa/rtTAA/TRE-N1-IC cell line.

Validation of MYC-driven drug responses.

Regression analysis showing the positive correlation between number of months since the prior chemotherapy regimen (X axis) and the difference between.

Expression of chemokine receptors in A-498 cell line.

High nuclear β-catenin levels confer resistance to AKT inhibition and coordinates with increased nuclear FOXO3a to promote metastasis in colon cancer.

Mechanism by which flavopiridol induces cell cycle arrest and apoptosis in rhabdoid tumor cells. Mechanism by which flavopiridol induces cell cycle arrest.

HER2 and PI3K-targeted therapies result in FOXO3a-mediated feedback upregulation of HER3 and IGF1R and provide an escape from PI3K pathway inhibition.

An isogenic cell line screen reveals genomic drivers of drug response.

THZ1 in combination with targeted therapy enhances cell death and hinders the establishment of drug-resistant colonies in diverse oncogene-addicted cellular.

Effects of inhibitors of PI3K, MEK1, and GSK-3β on visfatin-induced proliferation in HepG2 cells. Effects of inhibitors of PI3K, MEK1, and GSK-3β on visfatin-induced.

Identification and characterization of activated integrin pathway module by signal transduction representation (A) and unsupervised hierarchical clustering.

Synthetic lethality of ROS1 inhibition in E-cadherin–deficient breast tumor cell lines. Synthetic lethality of ROS1 inhibition in E-cadherin–deficient.

TRK inhibitor binding to acquired resistance mutations.

Presentation transcript:

High-throughput drug screen (HTDS) reveals ARS1620 and PI3K pathway inhibitors synergies and a heterogeneous pattern of RTK synergies. High-throughput drug screen (HTDS) reveals ARS1620 and PI3K pathway inhibitors synergies and a heterogeneous pattern of RTK synergies. A, Pie chart of 112 drugs: color code corresponds to hit target type. B, Top hits identified across 112 drugs tested in combination with ARS1620. Only combinations yielding at least 1 instance of a 5-fold shift in IC50 in the presence of ARS1620 over single agent are presented. C, Pattern of a selected panel of recurrent effective combination across cell lines. IC50 shift (median across biological replicates) is shown. Sandra Misale et al. Clin Cancer Res 2019;25:796-807 ©2019 by American Association for Cancer Research