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Total 64 results found since Jan 2013.
Abstract 4999: Signaling-associated complexes to define targetable vulnerabilities in lung cancer
Lung cancer is the leading cause of cancer related death in the U.S. Despite successes targeting tyrosine kinase drivers such as EGFR and EML4-ALK, identification of patients who will benefit from emerging targeted therapy regimens remains a challenge. This is exemplified by the disappointing results in the recent Phase III evaluation of ornatuzumab in combination with erlotinib in advanced non-small cell lung cancer (NCT01456324), targeting both MET and EGFR in biomarker-defined patient populations. We have previously shown that proximity ligation assay (PLA) technology can be harnessed to evaluate EGFR pathway activation...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Smith, M., Licata, T., Bai, Y., Zhang, G., Vuaroqueaux, V., Fiebig, H.-H., Haura, E. B. Tags: Molecular and Cellular Biology Source Type: research
Nuclear EGFR renders cells radio-resistant by binding mRNA species and triggering a metabolic switch to increase lactate production.
CONCLUSIONS: We showed that nuclear EGFR selectively binds and stabilizes mRNA involved in the Warburg effect in response to irradiation. As a consequence, cells switch from aerobic to anaerobic glucose metabolism, which can be prevented by HIF1α inhibitor BAY87-2243, Dasatinib, Erlotinib or EGFR siRNA.
PMID: 26320552 [PubMed - as supplied by publisher]
Source: Radiotherapy and Oncology : journal of the European Society for Therapeutic Radiology and Oncology - August 27, 2015 Category: Radiology Authors: Dittmann K, Mayer C, Paasch A, Huber S, Fehrenbacher B, Schaller M, Rodemann HP Tags: Radiother Oncol Source Type: research
Quantitative proteomics unveiled: Regulation of DNA double strand break repair by EGFR involves PARP1.
CONCLUSION: We have established a powerful, quantitative phosphoproteomic approach to investigate regulatory mechanisms in DSB repair, dependent on protein phosphorylation after irradiation. Using this approach we have identified PARP1 as a mediator of EGFR/MEK-dependent regulation of DSB repair.
PMID: 26422459 [PubMed - as supplied by publisher]
Source: Radiotherapy and Oncology : journal of the European Society for Therapeutic Radiology and Oncology - September 25, 2015 Category: Radiology Authors: Myllynen L, Kwiatkowski M, Gleißner L, Riepen B, Hoffer K, Wurlitzer M, Petersen C, Dikomey E, Rothkamm K, Schlüter H, Kriegs M Tags: Radiother Oncol Source Type: research
Abstract A65: A novel regulatory mechanism involving Ras-mediated activation of the zinc-finger transcription factor, SAF-1/MAZ induces EGFR/HER1 expression in breast cancer cells
Tumor microenvironment (TME) plays a critical role in tumor growth, invasion and metastasis. In TME, epidermal growth factor receptor (EGFR) family members, including HER1, HER2, HER3 and HER4, are involved in determining aggressive growth of breast cancer due to their ability to transduce the growth promoting functions of growth factors. This activity is potentiated by the over-expression of these receptor molecules in cancer cells. To reduce the activity of EGFR molecules, various inhibitors have been developed. EGFR/HER1 tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, show antitumor activity but these drugs ...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Ray, A., Havis, B., Ray, B. Tags: EGFR / Her2: Poster Presentations - Proffered Abstracts Source Type: research
Targeting non-canonical autophagy overcomes erlotinib resistance in tongue cancer
In this report, we found that autophagy prior to or induced by erlotinib treatment plays an important role in erlotinib resistance in tongue cancer cells. Using LC3 transfection, we observed that autophagy is upregulated and further induced when treated with erlotinib. Moreover, we found that autophagy plays a cytoprotective role by MTT analysis of the cell viability in TSCCs when treated with rapamycin or hydroxychloroquine (HCQ) in combination with erlotinib. However, 3-methyladenine (3-MA) did not influence the autophagy. Then, through siRNA technology and WB, we found that erlotinib-induced autophagy is mediated by ATG...
Source: Tumor Biology - January 21, 2016 Category: Cancer & Oncology Source Type: research
MAPK1E322K mutation increases head and neck squamous cell carcinoma sensitivity to erlotinib through enhanced secretion of amphiregulin.
In this study, we investigated the mechanism of MAPK1E322K-mediated EGFR activation in the context of erlotinib sensitivity. We demonstrated increased AREG secretion in HNSCC cell lines harboring endogenous or exogenous MAPK1E322K compared to wild type MAPK1. We found inhibition or knockdown of MAPK1 with siRNA resulted in reduced secretion of AREG and decreased sensitivity to erlotinib in the setting of MAPK1E322K. MAPK1E322K was associated with increased AREG secretion leading to an autocrine feedback loop involving AREG, EGFR and downstream signaling. Knockdown of AREG in HNSCC cells harboring MAPK1E322K abrogated EGFR ...
Source: Oncotarget - March 25, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Autophagy inhibition facilitates erlotinib cytotoxicity in lung cancer cells through modulation of endoplasmic reticulum stress.
In this study, we found the sensitivity to erlotinib, a well-used EGFR-TKI, was correlated with basal autophagy level. Erlotinib was able to induce autophagy not only in TKI-sensitive, but also TKI-resistant cancer cells. Inhibition of autophagy significantly enhanced cytotoxicity of erlotinib in TKI-resistant cancer cells via modulation of endoplasmic reticulum (ER) stress induced apoptosis. In this process, CCAAT/enhancer binding protein homologous protein (CHOP) acted as an executioner. Downregulation of CHOP with siRNA blocked the autophagy inhibition and erlotinib co-treatment induced apoptosis and prevented cancer ce...
Source: International Journal of Oncology - March 31, 2016 Category: Cancer & Oncology Authors: Wang Z, Du T, Dong X, Li Z, Wu G, Zhang R Tags: Int J Oncol Source Type: research
Interaction of the EGF Receptor and the Hippo Pathway in the Diabetic Kidney
Activation of the EGF receptor (EGFR) or the Hippo signaling pathway can control cell proliferation, apoptosis, and differentiation, and the dysregulation of these pathways can contribute to tumorigenesis. Previous studies showed that activation of EGFR signaling in renal epithelial cells can exacerbate diabetic kidney injury. Moreover, EGFR has been implicated in regulating the Hippo signaling pathway in Drosophila; thus, we examined this potential interaction in mammalian diabetic kidney disease. Yes-associated protein (YAP) is a transcriptional regulator regulated by the Hippo signaling pathway. We found YAP protein exp...
Source: Journal of the American Society of Nephrology : JASN - May 30, 2016 Category: Urology & Nephrology Authors: Chen, J., Harris, R. C. Tags: Basic Research Source Type: research
Mechanism of c-Met and EGFR tyrosine kinase inhibitor resistance through epithelial mesenchymal transition in non-small cell lung cancer.
Abstract
According to Cancer Research UK currently available estimates, 14.1 million new lung cancer cases were diagnosed and a staggering 8.2 million people worldwide died from lung cancer in 2012. EGFR and c-Met are two tyrosine kinase receptors most commonly overexpressed or mutated in Non-small Cell Lung Cancer (NSCLC) resulting in increased proliferation and survival of lung cancer cells. Tyrosine kinase inhibitors (TKIs), such as Erlotinib, approved by the FDA as first/second line therapy for NSCLC patients have limited clinical efficacy due to acquired resistance. In this manuscript, we investigate and disc...
Source: Biochemical and Biophysical Research communications - July 6, 2016 Category: Biochemistry Authors: Rastogi I, Rajanna S, Webb A, Chhabra G, Foster B, Webb B, Puri N Tags: Biochem Biophys Res Commun Source Type: research
In Vitro and In Vivo Synergistic Antitumor Activity of the Combination of BKM120 and Erlotinib in Head and Neck Cancer: Mechanism of Apoptosis and Resistance
This study investigated whether cotargeting of EGFR and PI3K has synergistic antitumor effects and apoptosis induction. We examined growth suppression, apoptosis, and signaling pathway modulation resulting from single and combined targeting of EGFR and PI3K with erlotinib and BKM120, respectively, in a panel of SCCHN cell lines and a xenograft model of SCCHN. In a panel of 12 cell lines, single targeting of EGFR with erlotinib or PI3K with BKM120 suppressed cellular growth without inducing significant apoptosis. Cotargeting of EGFR and PI3K synergistically inhibited SCCHN cell line and xenograft tumor growth, but induced v...
Source: Molecular Cancer Therapeutics - April 2, 2017 Category: Cancer & Oncology Authors: Anisuzzaman, A. S. M., Haque, A., Wang, D., Rahman, M. A., Zhang, C., Chen, Z., Chen, Z. G., Shin, D. M., Amin, A. R. M. R. Tags: Cancer Biology and Signal Transduction Source Type: research
Salinomycin acts through reducing AKT-dependent thymidylate synthase expression to enhance erlotinib-induced cytotoxicity in human lung cancer cells.
In this study, we showed that erlotinib (1.25 - 10μM) treatment down-regulating of TS expression in an AKT inactivation manner in two NSCLC cell lines, human lung squamous cell carcinoma H1703 and adenocarcinoma H1975 cells. Knockdown of TS using small interfering RNA (siRNA) or inhibiting AKT activity with PI3K inhibitor LY294002 enhanced the cytotoxicity and cell growth inhibition of erlotinib. A combination of erlotinib and salinomycin resulted in synergistic enhancement of cytotoxicity and cell growth inhibition in NSCLC cells, accompanied with reduced protein levels of phospho-AKT(Ser473), phospho-AKT(Thr308), and TS...
Source: Experimental Cell Research - April 25, 2017 Category: Cytology Authors: Tung CL, Chen JC, Wu CH, Peng YS, Chen WC, Zheng HY, Jian YJ, Wei CL, Cheng YT, Lin YW Tags: Exp Cell Res Source Type: research
Estrogen receptor β1 activation accelerates resistance to epidermal growth factor receptor-tyrosine kinase inhibitors in non-small cell lung cancer.
In conclusion, ERβ1 was activated in EGFR-TKI secondary resistance. The downregulation of ERβ1 sensitized the cells to EGFR-TKIs. ERβ1 may be a key molecule in EGFR-TKI therapy. In addition, anti-ERβ1 treatment may reverse TKI resistance.
PMID: 29328407 [PubMed - as supplied by publisher]
Source: Oncology Reports - January 14, 2018 Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
Comparison of epithelial mesenchymal transition mediated tyrosine kinase inhibitor resistance in non-small cell lung cancer cell lines with wild type EGFR and mutant type EGFR.
This study investigates the role of epithelial-mesenchymal transition (EMT) in the development of resistance against TKIs in NSCLC. Currently, the role of p120-catenin, Kaiso factor and PRMT-1 in reversal of EMT in T790M mutated and TKI-resistant NSCLC cells is a new line of study. In this investigation we found upregulation of cytoplasmic p120-catenin, and it was co-localized with Kaiso factor. In the nucleus, binding of p120-catenin to Kaiso factor initiates transcription by activating EMT-transcription factors such as Snail, Slug, Twist, and ZEB1. PRMT-1 was also found to be upregulated, which induces methylation of Twi...
Source: Biochemical and Biophysical Research communications - January 11, 2018 Category: Biochemistry Authors: Iderzorig T, Kellen J, Osude C, Singh S, Woodman JA, Garcia C, Puri N Tags: Biochem Biophys Res Commun Source Type: research
Inositol trisphosphate receptor type 3-mediated enhancement of EGFR and MET co-targeting efficacy in non-small cell lung cancer detected by 18F-fluorothymidine.
CONCLUSIONS: Our findings indicate that 18F-FLT PET/CT is able to detect the enhanced efficacy of EGFR and MET inhibitors in oncogene-driven NSCLC and that such enhancement is mediated by IP3R3 through its interaction with K-Ras.
PMID: 29618618 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - April 4, 2018 Category: Cancer & Oncology Authors: Iommelli F, De Rosa V, Terlizzi C, Monti M, Panico M, Fonti R, Del Vecchio S Tags: Clin Cancer Res Source Type: research
Novel drug-resistance mechanisms of pemetrexed-treated non-small cell lung cancer.
In this study, we explored new drug resistance mechanisms of PEM-treated NSCLC using two combinations of parental and PEM-resistant NSCLC cell lines from PC-9 and A549. PEM increased the apoptosis cells in parental PC-9 and the senescent cells in parental A549. However, such changes were not observed in the respective PEM-resistant cell lines. Quantitative RT-PCR analysis revealed that, besides an increased gene expression of thymidylate synthase in PEM-resistant PC-9 cells, the solute carrier family 19 member1 (SLC19A1) gene expression was markedly decreased in PEM-resistant A549 cells. The siRNA-mediated knockdown of SLC...
Source: Oncotarget - April 25, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
