Köse Meryem
PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.
Bioorg Med Chem Lett. 2017 Aug 15;27(16):3611-3620. doi: 10.1016/j.bmcl.2017.07.002. Epub 2017 Jul 3.
G protein-coupled receptors (GPCRs) and receptor-tyrosine kinases (RTKs) are two important classes of cell surface receptors proven to be highly tractable as drug targets. Both receptor classes are involved in various complex (patho-) physiological processes in the human body including cellular growth and differentiation. More recently, accumulating data suggest that GPCR-induced activation of EGFR, the prototyp of RTKs represents a major mechanism in various cancers. The present review will focus on this cross-talk with particular emphasis on intracellular scaffold proteins regulating EGFR transactivation. It will give an overview about the current status of the research and future directions, highlight recent trends in the field, and discuss the potential of therapeutic strategies combining GPCR and EGFR targeting on the one hand and specific targeting of the cross-talk on the other hand in cancer therapy.
G蛋白偶联受体(GPCRs)和受体酪氨酸激酶(RTKs)是两类重要的细胞表面受体,已被证明作为药物靶点具有很高的可操作性。这两类受体都参与人体各种复杂的(病理-)生理过程,包括细胞生长和分化。最近,越来越多的数据表明,GPCR诱导的RTKs原型表皮生长因子受体(EGFR)激活是各种癌症中的一种主要机制。本综述将聚焦于这种相互作用,特别强调调节EGFR反式激活的细胞内支架蛋白。它将概述该研究的现状和未来方向,突出该领域的最新趋势,并讨论一方面联合靶向GPCR和EGFR、另一方面特异性靶向这种相互作用的治疗策略在癌症治疗中的潜力。