Growth factor receptor inhibitor

About: Growth factor receptor inhibitor is a research topic. Over the lifetime, 4730 publications have been published within this topic receiving 297500 citations.

Failure of the bovine papillomavirus to transform mouse embryo fibroblasts with a targeted disruption of the insulin-like growth factor I receptor genes.

Abstract: Mouse embryo cells with a targeted disruption of the insulin-like growth factor I receptor (IGF-IR) genes (R- cells) are refractory to transformation by the simian virus 40 large T antigen and/or an activated and overexpressed Ras, both of which readily transform cells from wild-type littermate embryos and other 3T3-like cells. R- cells are also refractory to transformation induced by overexpressed epidermal growth factor receptor and platelet-derived growth factor receptor beta. Since the platelet-derived growth factor receptor beta is required for transformation by bovine papillomavirus, we inquired whether the IGF-IR was also required for transformation by bovine papillomavirus E5 oncoprotein. We show here that R- cells are refractory to transformation by E5; reintroduction into R- cells of a human IGF-IR restores the susceptibility to transformation.

miR-7 inhibits the invasion and metastasis of gastric cancer cells by suppressing epidermal growth factor receptor expression.

Abstract: The present study profiled differentially expressed microRNAs (miRs) in gastric cancer cell lines and then investigated miR-7 expression in gastric cancer tissue specimens and the effects of miR-7 on the growth, invasion and metastasis of gastric cancer cells and the underlying molecular events. A microRNA microarray was used to profile differentially expressed miRNAs in human gastric cancer cell lines relative to a normal stomach mucosal epithelial cell line. The miRNA miR-7 was selected for further investigation, which included real-time reverse-transcription PCR (qRT-PCR) analysis of miR-7 levels in different gastric cancer cell lines and tissues and distant non-tumor tissues from patient resections. Cell counting kit-8 (CCK-8), Transwell migration and invasion, and western blot assays were performed to assess tumor cell viability, invasion and gene expression, respectively, after miR-7 transfection. The miRNA microarray profiling revealed 14 upregulated miRNAs (including miR-21, miR-26b and miR-30b) and 19 downregulated miRNAs (including let-7i, miR-7 and miR-622) between gastric cancer and normal cell lines. The qRT-PCR analysis confirmed that reduced miR-7 expression occurred more frequently in poorly and moderately differentiated gastric cancer MGC-803, MKN-45 and SGC-7901 cell lines than in the well-differentiated gastric cancer NCI-N87 cell line, which was consistent with the results for gastric cancer tissues. Expression of miR-7 was downregulated in 86.9% (20/23) of the gastric cancer tissues compared with that in the distant non-tumor tissues. Restoration of miR-7 expression significantly inhibited tumor cell viability, invasiveness and migration when compared with the control cells. Luciferase assay confirmed the epidermal growth factor receptor (EGFR) as a target gene of mR-7, and expression of miR-7 significantly suppressed EGFR expression at both the mRNA and protein levels. The data from the present study demonstrated that reduced miR-7 expression contributes to gastric cancer development and progression. Further study will investigate miR-7 in the regulation of EGFR expression in vitro and in vivo.

The role of cetuximab in the treatment of squamous cell cancer of the head and neck

Abstract: The epidermal growth factor receptor (EGFR) is a member of the HER family of tyrosine kinase growth factor receptors. Binding to EGFR by its natural ligands, mainly epidermal growth factor (EGF) or transforming growth factor (TGF)-alpha, results in a conformational change in the receptor, which promotes homo- or heterodimerisation or oligomerisation with other EGFR molecules or other HER family members. Dimerisation results in the activation of intracellular tyrosine kinase, autophosphorylation and activation of signal transduction molecules, ultimately leading to cell cycle progression, reduced apoptotic capacity, angiogenesis and the metastatic phenotype. EGFR is expressed on normal human cells and also across a range of malignancies. Tumour EGFR expression correlates with poor prognosis and resistance to therapy. Cetuximab is a chimeric human:murine monoclonal antibody that binds competitively to the EGFR. Binding of the antibody to the EGFR prevents activation of the receptor by endogenous ligands; proliferation is reduced, apoptosis enhanced, and angiogenesis, invasiveness and metastasis reduced. Binding of cetuximab to the receptor also results in internalisation and degradation of the antibody-receptor complex, downregulating EGFR expression. EGFR has been recognised as an important therapeutic target in cancer. Other antibodies are also in development, and small molecular inhibitors of the tyrosine kinase domain are available. Cetuximab adds to the activity of radiotherapy in locoregional head and neck cancer, and when given with platinum-based chemotherapy is active in a proportion of patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck, as is cetuximab monotherapy. When cetuximab is added to cisplatin monotherapy in the first-line treatment of recurrent or metastatic squamous cell carcinoma of the head and neck, the objective response rate is significantly improved and the hazard ratio for progression is 0.78. The most commonly reported adverse event associated with cetuximab treatment is an acneiform rash that occurred in 70 - 80% of patients treated with cetuximab. Presence of the characteristic rash is significantly associated with response and/or survival. It is possible that development of acneiform rash may become an important clinical prognostic marker. Serious cetuximab-related toxicities include hypersensitivity reactions. Thus, cetuximab is biologically active across a range of clinical scenarios in squamous cell carcinoma of the head and neck. Ongoing studies will be important in establishing its role in the routine management of head and neck cancer.