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.

Tyrosine Kinase Inhibitors of Vascular Endothelial Growth Factor Receptors in Clinical Trials: Current Status and Future Directions

Abstract: Angiogenesis plays a central role in the process of tumor growth and metastatic dissemination. The vascular endothelial growth factor (VEGF) family of peptide growth factors and receptors are key regulators of this process. Agents directed either against VEGF or VEGF receptors (VEGFRs) have been developed. The tyrosine ksnorVEGFRs are low-molecular-weight ATP-mimetic proteins that bind to the ATP-binding catalytic site of the tyrosine kinase domain of VEGFRs, resulting in blockade of intracellular signaling. Several of these agents are currently in different phases of clinical development. Large randomized phase III trials have demonstrated the efficacy of sunitinib and sorafenib in the treatment of patients affected by gastrointestinal stromal tumors and renal cancer refractory to standard therapies, respectively. Positive results also have been reported with the combination of ZD6474 and chemotherapy in previously treated nonsmall cell lung cancer patients. For other agents, such as vatalanib, contrasting outcomes in metastatic colorectal cancer patients have been reported: the final results of these trials are expected in 2006. However, several key questions remain to be addressed, regarding the choice o andeque dos or schdul, th presne of “of-target” effects, the safety of long-term administration, and the research of new clinical end points or methodological approaches for the optimal clinical development of these agents. The Oncologist 2006;11:753–764

Fibroblast growth factors and their receptors

Abstract: Fibroblast growth factors (FGFs) represent a group of polypeptide mitogens eliciting a wide variety of responses depending upon the target cell type. The knowledge of the cell surface receptors mediating the effects of FGFs has recently expanded remarkably. The complexity of the FGF family and the FGF-induced responses is reflected in the diversity and redundancy of the FGF receptors. In this review, a number of biochemical characteristics and biological properties of the FGF family and its receptors are described and their expression both in normal tissues and in tumours is discussed. Finally we speculate on the targetting of growth inhibition agents to tumours through FGF receptors.

Epidermal growth factor stimulates transcription of the c-jun proto-oncogene in rat fibroblasts

Abstract: Some growth factor-induced genes, such as the c-fos gene, are activated rapidly and transiently without intervening protein synthesis. Others, like the rat transin gene, are activated more slowly but more durably and their activation requires prior protein synthesis. It is tempting to speculate that certain rapidly-activated genes code for transcription factors which interact directly with promoter regions of genes like the transin gene to trigger their expression. Unfortunately, little is known about the majority of primary response genes to support this hypothesis. The proto-oncogene c-jun codes for the transcription factor AP-1 or a closely related protein. We show that epidermal growth factor stimulates transcription of the c-jun gene in fibroblasts as a primary response. This supports the notion that increased expression of genes encoding transcription factors is an important element of the signal transduction mechanism, assuring the long-term transcriptional response of cells to growth factors.

Cell-free activation of a DNA-binding protein by epidermal growth factor

Abstract: GROWTH factors such as platelet-derived growth factor and epidermal growth factor (EGF) bind to and activate cell-surface receptors with intrinsic tyrosine kinase activities1. Receptor activation elicits multiple physiological changes in target cells, including alterations in gene expression2–4. Receptor tyrosine kinase signalling involves recruitment of proteins into a signalling complex through interactions between receptor autophosphorylation sites and the src-homology region-2 (SH2) domains on these signalling proteins5–9. Diverse signals can subsequently be generated, depending on the specific receptor and cell type2,10. How such signals are transmitted to the nucleus is poorly understood, but because the transcriptional activation of many genes by growth factors occurs in the absence of new protein synthesis4, one or more signals emanating from growth factor receptors must directly affect transcription factors. We report here the activation by EGF of a DNA-binding protein in a cell-free system where activation of DNA binding requires ligand, receptor, ATP and phosphotyrosine–SH2 interactions.