Last update 01 Nov 2024

EGFR x CCR1

Last update 01 Nov 2024

Basic Info

Related Targets

EGFRCCR1

Drugs associated with EGFR x CCR1

OV-Cmab-CCL5

Target

CCR1 x EGFR

Mechanism

CCR1 modulators [+1]

Active Org.

City of Hope National Medical Center

Originator Org.

City of Hope National Medical Center

Active Indication

Glioblastoma

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with EGFR x CCR1

100 Translational Medicine associated with EGFR x CCR1

0 Patents (Medical) associated with EGFR x CCR1

Literatures (Medical) associated with EGFR x CCR1

01 Jan 2015·Biological & Pharmaceutical BulletinQ4 · MEDICINE

Molecular Targeted Therapy for Hepatocellular Carcinoma: Present Status and Future Directions

Q4 · MEDICINE

Review

Author: Choi, Kyung-Ju ; Ye, Sang-Kyu ; Baik, In Hye ; Lee, Yun-Han

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most lethal neoplasm, causing an estimated 700000 deaths annually. Currently HCC has only one systemic molecular targeted therapy, the multi-kinase inhibitor, sorafenib. The standard-of-care for advanced liver cancer is limited because sorafenib can expand the median life expectancy of patients for only 1 year. Thus there is an urgent need to develop a novel molecular targeted therapy to improve therapeutic outcomes for HCC. HCCs are phenotypically and genetically heterogeneous tumors driven by diverse molecular mechanisms. However, HCCs exhibit certain common traits selected through genetic and epigenetic alterations. The identification of common molecular alterations may provide an opportunity to develop more effective anticancer treatment through targeted therapy. Recent studies in liver cancer biology have revealed a limited number of molecular targets responsible for initiating and maintaining dysregulated cell proliferation, including vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR), c-mesenchymal-epithelial transition factor-1 (c-Met), mammalian target of rapamycin (mTOR) and histone deacetylases (HDACs). New treatments involving inhibitors targeting several of these critical pathways are in development. This review describes the current understanding of target pathways, ongoing clinical trials using HCC-targeted agents, and future directions in the treatment of HCC.

01 Jan 2009·Molecular CancerQ1 · MEDICINE

Transcriptomic analysis of pathways regulated by toll-like receptor 4 in a murine model of chronic pulmonary inflammation and carcinogenesis

Q1 · MEDICINE

ArticleOA

Author: Sherry F Grissom ; Elizabeth A Rondini ; Alison K Bauer ; Christopher Walker ; Laura M Degraff ; Steven R Kleeberger ; Julie Foley ; Jennifer Fostel

BACKGROUNDTherapeutic strategies exist for human pulmonary neoplasia, however due to the heterogeneity of the disease, most are not very effective. The innate immunity gene, toll-like receptor 4 (TLR4), protects against chronic pulmonary inflammation and tumorigenesis in mice, but the mechanism is unclear. This study was designed to identify TLR4-mediated gene expression pathways that may be used as prognostic indicators of susceptibility to lung tumorigenesis in mice and provide insight into the mechanism.METHODSWhole lung mRNA was isolated from C.C3H-Tlr4(Lps-d) (BALB(Lps-d); Tlr4 mutant) and BALB/c (Tlr4 normal) mice following butylated hydroxytoluene (BHT)-treatment (four weekly ip. injections; 150-200 mg/kg/each; "promotion"). mRNA from micro-dissected tumors (adenomas) and adjacent uninvolved tissue from both strains were also compared 27 wks after a single carcinogen injection (3-methylcholanthrene (MCA), 10 microg/g; "control") or followed by BHT (6 weekly ip. injections; 125-200 mg/kg/each; "progression"). Bronchoalveolar lavage fluid was analyzed for inflammatory cell content and total protein determination, a marker of lung hyperpermeability; inflammation was also assessed using immunohistochemical staining for macrophages (F4/80) and lymphocytes (CD3) in mice bearing tumors (progression).RESULTSDuring promotion, the majority of genes identified in the BALB(Lps-d) compared to BALB/c mice (P < 0.05) were involved in epithelial growth factor receptor (EGFR) signaling (e.g. epiregulin (Ereg)), secreted phosphoprotein 1(Spp1)), which can lead to cell growth and eventual tumor development. Inflammation was significantly higher in BALB(Lps-d) compared to BALB/c mice during progression, similar to the observed response during tumor promotion in these strains. Increases in genes involved in signaling through the EGFR pathway (e.g. Ereg, Spp1) were also observed during progression in addition to continued inflammation, chemotactic, and immune response gene expression in the BALB(Lps-d) versus BALB/c mice (P < 0.05), which appears to provide more favorable conditions for cell growth and tumor development. In support of these findings, the BALB/c mice also had significantly reduced expression of many immune response and inflammatory genes in both the tumors and uninvolved tissue.CONCLUSIONThis transcriptomic study determined the protective effect of TLR4 in lung carcinogenesis inhibition of multiple pathways including EGFR (e.g. Ereg), inflammatory response genes (e.g. Cxcl5), chemotaxis (e.g. Ccr1) and other cell proliferation genes (e.g. Arg1, Pthlh). Future studies will determine the utility of these pathways as indicators of immune system deficiencies and tumorigenesis.

01 Oct 2007·International Journal of CancerQ1 · MEDICINE

Overexpression of ErbB2 in the exocrine pancreas induces an inflammatory response but not increased proliferation

Q1 · MEDICINE

Article

Author: Marina Lesina ; Roland M. Schmid ; Martin Wagner ; Hana Algül

AbstractTyrosine kinase receptors such as members of the epidermal growth factor receptor family and their respective ligands are frequently overexpressed in pancreatic cancer as well as in chronic pancreatitis. In this study, the role of ErbB2 in the exocrine pancreas was examined by ectopic overexpression under the control of the proximal rat elastase promoter. Three independent transgenic mouse lines overexpressing ErbB2 were established by pronuclear injection. Pancreatic mRNA and protein levels were analyzed by real time PCR, immunohistochemistry and immunoblot analysis, RAS activity by using a specific immunoprecipitation assay and various kinase activities by phosphospecific antibodies. Overexpression of ErbB2 in the exocrine pancreas resulted in increased RAS activity and downstream activation of ERK1/2, but not in transgenic increased proliferation of acinar and ductal cells. At later timepoints, some mice showed focal areas of acinar cell damage with upregulated mRNA levels for Cyclin D1 and p16INK4a. Despite the increased mRNA level, cyclin D1 protein levels were downregulated. We observed areas of focal infiltrations with inflammatory cells interspersed in the exocrine pancreas. NF‐κB activity was induced in transgenic acinar cells compared with controls contributing to high levels of chemokine and cytokine gene expression such as CCR‐1 and CCL3. These data suggest that overexpression of ErbB2 in acinar cells leads to increased RAS activity without cell cycle progression and mediates inflammation via NF‐κB. We conclude that the biological response of ErbB2/RAS signaling depends highly on cellular context. © 2007 Wiley‐Liss, Inc.

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