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One of the major mediators of multidrug resistance (MDR) in non-small cell lung cancer (NSCLC) is the overexpression of ATP-binding cassette subfamily G member 2 (ABCG2). In this study, we conducted in vitro and in vivo experiments to determine whether PD153035, an inhibitor of EGFR, could reverse ABCG2-mediated MDR in human NSCLC and transfected cells overexpressing ABCG2. The efficacy of SN-38, topotecan, and mitoxantrone (MX) was significantly increased by PD153035, PD153035 significantly reversed ABCG2-mediated MDR by attenuating the efflux activity of this transporter. In addition, PD153035 significantly down-regulated the expression of the ABCG2 transporter protein. Furthermore, a combination of PD153035 and topotecan, exhibited significant synergistic anticancer activity against mice xenografted with human H460/MX20 cells. These results, provided that they can be extrapolated to humans, suggest that the combination of topotecan and PD153035 could be a promising therapeutic strategy to attenuate the resistance to topotecan, as well as other anticancer drugs, mediated by the overexpression of ABCG2.
This article was published in the following journal.
Name: Cancer letters
The third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) osimertinib has been approved in many countries to treat advanced non-small cell lung cancer (NSCLC) in patie...
T790M is a major cause of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance, but the clinical significance of T790M disappearance is unknown.
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In this trial, treatment efficacy and safety of retreatment with 1st generation epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TKI)s(Gefitinib/Erlotinib), will be assesse...
RATIONALE: Studying samples of tissue and blood in the laboratory from patients with cancer receiving epidermal growth factor receptor (EGFR) inhibitors may help doctors understand the eff...
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Patient with Non-Small Cell Lung Cancer (NSCLC) that might have a genetic change (mutation) in the Epidermal Growth Factor Receptor (EGFR) are invited to take part in this study. This res...
A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF related peptides including TRANSFORMING GROWTH FACTOR ALPHA, amphiregulin, and heparin-binding EGF-like growth factor. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.
A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. EPIDERMAL GROWTH FACTOR exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells.
A fibroblast growth factor receptor that is found in two isoforms. One receptor isoform is found in the MESENCHYME and is activated by FIBROBLAST GROWTH FACTOR 2. A second isoform of fibroblast growth factor receptor 2 is found mainly in EPITHELIAL CELLS and is activated by FIBROBLAST GROWTH FACTOR 7 and FIBROBLAST GROWTH FACTOR 10. Mutation of the gene for fibroblast growth factor receptor 2 can result in APERT SYNDROME.
Retrovirus-associated DNA sequences (erbB) originally isolated from, or related to, the avian erythroblastosis virus (AEV). These genes code for the epidermal growth factor receptor (EGFR) family of receptors which is important in the control of normal cell proliferation and in the pathogenesis of human cancer. The genes include erbB-1 (GENES, ERBB-1), erbB-2 (GENES, ERBB-2), and erbB-3, all of which show abnormalities of expression in various human neoplasms.
A cell surface protein-tyrosine kinase receptor that is specific for NEUREGULINS. It has extensive homology to and can heterodimerize with the EGF Receptor (RECEPTOR, EPIDERMAL GROWTH FACTOR) and the erbB-2 receptor (RECEPTOR, ERBB-2). Overexpression of the erbB-3 receptor is associated with tumorigenesis.
GILOTRIF (afatinib) is a kinase inhibitor indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L8...
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...