ERK reactivation following EGFR TKI treatment.

Slides:

Advertisements

Similar presentations

AZD9291 inhibits EGFR phosphorylation and downstream signaling in murine models of EGFRT790M-resistant lung cancer. AZD9291 inhibits EGFR phosphorylation.

Advertisements

Inhibition of PDGFR-β downstream signaling events by flavones.

Combined RAF and EGFR inhibition leads to improved in vivo efficacy in BRAF-mutant colorectal cancer. Combined RAF and EGFR inhibition leads to improved.

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

PI3K isoform–selective inhibitors and PTEN induction decrease ERK phosphorylation. PI3K isoform–selective inhibitors and PTEN induction decrease ERK phosphorylation.

DNA-damage (γ-H2AX) and telomere damage–induced foci (TIFs).

Combined inhibition of MAP kinase and KIT signaling destabilizes ETV1 protein and results in enhanced growth suppression of human GIST cells. Combined.

CHK1 downregulation upon ERG overexpression.

NF1 downregulation activates MAPK pathway signaling.

The EGF receptor confers BRAF inhibitor resistance in BRAF-mutant melanoma cells. The EGF receptor confers BRAF inhibitor resistance in BRAF-mutant melanoma.

APC/C dysfunction results in CIN buffering and adaptation to extreme CIN. A and B, RPE1/H2B-mCherry cells were arrested in mitosis using 40 nmol/L STLC,

A, left: indicated MEFs were transfected as described in the Methods section. A, left: indicated MEFs were transfected as described in the Methods section.

Downregulation of SPRY4 expression is associated with FGFR1–FRS2 activation. Downregulation of SPRY4 expression is associated with FGFR1–FRS2 activation.

EGFR is intrinsically active in FGFR3-activated cell lines with combination efficacy from targeting both EGFR and FGFR3. EGFR is intrinsically active in.

Imipramine and promethazine induce the apoptotic cell death of SCLC cells through activation of caspase-3. Imipramine and promethazine induce the apoptotic.

BRAF inhibitor-resistant BRAF-mutant melanoma cells show increased invasion and metastatic potential. BRAF inhibitor-resistant BRAF-mutant melanoma cells.

Role of HER2 in mediating acquired resistance to EGFR inhibition.

AMPK induces VEGF-A production by upregulating ERK signaling.

CCL5 and IL-6 promote RAS-driven lung cancer cell proliferation in 3D culture. CCL5 and IL-6 promote RAS-driven lung cancer cell proliferation in 3D culture.

The role of SRC-C3G-RAP1 signaling in transformation induced by CRKL

AKT2, but not AKT1, is required for regulating survival of PTEN-deficient prostate tumor spheroids. AKT2, but not AKT1, is required for regulating survival.

Chronic PDGFRα activation reduces sensitivity of PDGFRα-positive GBM cells to translational inhibitor–induced suppression on cell viability. Chronic PDGFRα.

Allopurinol up-regulates DR5 expression in PC-3 and DU145 cells.

FeTTPS blocks tyrosine nitration of TrkA receptor and restores TrkA-Y490 phosphorylation in RGCs. A: Peroxynitrite (PN) increased TrkA tyrosine nitration.

BEZ235 induces MAPK signaling in a FOXO3A-dependent manner.

eNOS regulated IR-induced NO generation and EGFR signal activation.

BCR–ABL kinase activity rewires GM-CSFR signaling and confers oncogene addiction in TF1 cells. BCR–ABL kinase activity rewires GM-CSFR signaling and confers.

Inhibition of lung cancer cell proliferation and viability by CYT387.

GR cells are dependent upon sustained CDC25C signaling as pharmacologic or genetic inhibition of CDC25C induce synthetic lethality. GR cells are dependent.

G3139 substitutes for heparin, which is required for the biological activity of FGF2. G3139 substitutes for heparin, which is required for the biological.

Imatinib mesylate inhibits PDGF-mediated ERK and Akt activation.

Down-regulation of the erbB-2 receptor by trastuzumab decreases Akt kinase activation but not MAPK activation. Down-regulation of the erbB-2 receptor by.

Greater induction of apoptosis following EGFR TKI treatment correlates with higher basal BIM expression across a panel of EGFR-mutant lung cancers. Greater.

The effects of IAA and glycyrrhizin (Gc) on proliferation and cell-cycle distribution. The effects of IAA and glycyrrhizin (Gc) on proliferation and cell-cycle.

Effects of visfatin on the cell proliferation and phosphorylation of ERK, Akt, and GSK-3β proteins in HCC cells. Effects of visfatin on the cell proliferation.

Bcl-2 and caspase inhibition fails to inhibit BAMLET-induced cytotoxicity in MCF-7 cells. Bcl-2 and caspase inhibition fails to inhibit BAMLET-induced.

Discovery of Gö6976-related potent reversible EGFR T790M inhibitors.

A. A. Honokiol inhibits TNF-induced NF-κB activation, IκBα phosphorylation, and IκBα degradation. Honokiol inhibits TNF-induced activation of NF-κB. H1299.

MDA-468TR-PTEN (with and without 100 ng/ml doxycycline) and MDA-468TR-vector (with dox) were serum starved overnight and the following day treated for.

The AKT–mTOR pathway controls PD-L1 protein expression.

Inhibition of EGFR kinase activity and autophosphorylation by Iressa.

FACS analyses of the inhibitory effect induced by mixed docetaxel, gefitinib, and cyclopamine on EGF plus SHHNp–stimulated PC3 cells. FACS analyses of.

GR CAFs modulate the EGFR-TKI response in cocultured tumor cells.

The effect of different concentrations of WMC-79 and time of exposure on the growth of HCT-116 cells. The effect of different concentrations of WMC-79.

Combination of miR-520d-3p and EphA2 siRNA treatment shows enhanced EphA2 inhibition and antitumor efficiency in vitro. Combination of miR-520d-3p and.

Changes in signal transduction pathway induced by gefitinib.

HES1-dependent activation of SRC/STAT3 pathway is mediated by transcription-independent mechanism. HES1-dependent activation of SRC/STAT3 pathway is mediated.

EGFR signaling regulates transcription of PDGFRβ gene.

A combination of neurotensin and insulin potently decreases YAP phosphorylation at Ser127 and Ser397 in PDAC cells. A combination of neurotensin and insulin.

The combination of trastuzumab and SU11274 abrogate Akt phosphorylation. The combination of trastuzumab and SU11274 abrogate Akt phosphorylation. Serum-starved.

EMT alters activation of AKT and serum-independent proliferation.

A, effect of Z-VAD treatment on synchronized HeLa MR cells.

TBK1 signaling also promotes basal autophagy in 8988T cells.

A, cell number was assessed 96 hours after exposure to indicated treatment in indicated cell models. A, cell number was assessed 96 hours after exposure.

EGCG affects growth factor receptor signaling in H2111, H358, and H460 NSCLC cells. EGCG affects growth factor receptor signaling in H2111, H358, and H460.

AKT activation in HCC2429 is SRC- but not Notch-dependent.

A, left: LNCaP cells were cultured in media containing complete serum, treated for 24 hours with either ethanol control (0.01%), ABT888 (2.5 mmol/L), or.

Effect of MIF siRNA on the production of MMP-13 induced by LPA

Heterogeneous resistance mechanisms develop in response to W+T combination treatment in the EGFRL858R/T790M genetically engineered mice. Heterogeneous.

Blockade of cell cycle at G2-M phase in Bel-7402 cells treated with IG-105. Blockade of cell cycle at G2-M phase in Bel-7402 cells treated with IG-105.

LY elicits hyperphosphorylation of Akt.

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

MTOR kinase inhibition–induced reactivation of AKT substrates is HER2 and PI3K dependent. mTOR kinase inhibition–induced reactivation of AKT substrates.

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

A, indicated model systems were cultured in media containing complete serum, harvested, and lysed; total protein was separated by SDS-PAGE, transferred.

NVP-BGJ398 inhibits proliferation of a subset of cancer cell lines.

Curative effect of W+T treatment in vivo.

Afatinib rapidly destabilizes endogenous TRIB2 and specifically induces caspase 3 cleavage and U937 cytotoxicity. Afatinib rapidly destabilizes endogenous.

Inhibition of BCR-mediated signaling by ARQ 531.

AXL is not necessary for maintenance of intrinsic resistance.

Presentation transcript:

ERK reactivation following EGFR TKI treatment. ERK reactivation following EGFR TKI treatment. A, cells were treated with DMSO (media), 100 nmol/L WZ4002, 1 μmol/L of WZ4002, or 1 μmol/L gefitinib weekly (mean ± SD, n = biologic triplicates, 60 wells each). B, PC9 cells were treated with 1 μmol/L WZ4002 or 1 μmol/L gefitinib, and AKT and ERK1/2 phosphorylation (p) was assessed. HSP90 was assessed as a loading control. Image is representative of three independent experiments. C, cell lines were treated with 100 nmol/L WZ4002 (W), 30 nmol/L trametinib (T), or a combination thereof (C) for the indicated time, and phosphorylation of AKT and ERK1/2 was assessed by immunoblotting. Image is representative of two independent experiments. Erin M. Tricker et al. Cancer Discovery 2015;5:960-971 ©2015 by American Association for Cancer Research