Molecular targeting of growth factor receptor-bound 2 (Grb2) as an anti-cancer strategy.
Journal - Anti-cancer drugs (England )
Growth factor receptor-bound 2 (Grb2) is a ubiquitously expressed adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway. As such, it has been implicated in the oncogenesis of several important human malignancies. In addition to this function, research over the last decade has revealed other fundamental roles for Grb2 in cell motility and angiogenesis--processes that also contribute to tumor growth, invasiveness and metastasis. This functional profile makes Grb2 a high priority target for anti-cancer drug development. Knowledge of Grb2 protein structure, its component Src homology domains and their respective structure-function relationships has facilitated the rapid development of sophisticated drug candidates that can penetrate cells, bind Grb2 with high affinity and potently antagonize Grb2 signaling. These novel compounds offer considerable promise in our growing arsenal of rationally designed anti-cancer therapeutics.
|ISSN : ||0959-4973|
|Mesh Heading : ||Animals Antineoplastic Agents Drug Delivery Systems GRB2 Adaptor Protein Humans Neoplasms Signal Transduction metabolism drug therapy metabolism drug effects|
|Mesh Heading Relevant : ||pharmacology antagonists & inhibitors|
Hereditary papillary renal carcinoma type I.
Journal - Current molecular medicine (Netherlands )
Germline missense mutations in the tyrosine kinase domain of the hepatocyte growth factor/scatter factor (HGF/SF) receptor, c-Met, are thought to be responsible for hereditary papillary renal carcinoma (HPRC) type 1, a form of human kidney cancer. In addition to extensive linkage analysis of HPRC families localizing the HPRC type 1 gene within chromosome 7, the demonstration that individual c-Met mutations reconstituted in cultured cells display enhanced and dysregulated kinase activity, and confer cell transformation and tumorigenicity in mice, solidifies this conclusion. Our prior knowledge of HGF/SF biology and c-Met signaling enabled rapid progress in unraveling the molecular pathogenesis of HPRC type 1, and in laying the framework for the development of novel therapeutics for the treatment of this cancer. At the same time, the study of HPRC type 1 has refined our appreciation of the oncogenic potential of c-Met signaling, and challenges our current understanding of HGF/SF and c-Met function in health and disease.
|ISSN : ||1566-5240|
|Mesh Heading : ||Carcinoma, Papillary Cell Line, Tumor Humans Kidney Neoplasms Mutation Proto-Oncogene Proteins c-met classification classification|
|Mesh Heading Relevant : ||genetics genetics genetics|