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首页> 外文期刊>Archives of Toxicology >Epidermal growth factor receptor signalling in keratinocyte biology: Implications for skin toxicity of tyrosine kinase inhibitors
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Epidermal growth factor receptor signalling in keratinocyte biology: Implications for skin toxicity of tyrosine kinase inhibitors

机译:角质形成细胞生物学中的表皮生长因子受体信号转导:酪氨酸激酶抑制剂对皮肤毒性的影响

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The epidermal growth factor receptor (EGFR) and its ligands have been long recognized as centrally involved in the growth and repair process of epithelia, as well as in carcinogenesis. In addition, the EGFR has been demonstrated to be importantly involved in the control of inflammatory responses. During this last decade, a number of highly specific agents targeting this system have become an integral component of pharmacologic strategies against many solid malignancies. These drugs have led to increased patient survival and made therapy more tolerant when compared to conventional cytotoxic drugs. Nonetheless, their use is associated with a constellation of toxic effects on the skin, including follicular pustules, persistent inflammation, xerosis and pruritus, and enhanced susceptibility to infections. This dramatic impairment of skin homoeostasis underscores the centrality of the EGFR-ligand system in the whole skin immune system. So far, no mechanism-based approaches are available to specifically counteract the adverse effects of anti-EGFR drugs or any other class of tyrosine kinase inhibitors. Only the knowledge of the cellular and molecular events underlying these adverse effects in humans, combined with in vitro/in vivo models able to mimic these toxic responses, may guide the development of mechanism-based treatment or prevention strategies.
机译:长期以来,人们一直认为表皮生长因子受体(EGFR)及其配体主要参与上皮细胞的生长和修复过程以及癌变过程。另外,已经证明EGFR重要参与炎症反应的控制。在过去的十年中,针对该系统的许多高度特异性的药物已成为针对许多实体恶性肿瘤的药理策略不可或缺的组成部分。与传统的细胞毒性药物相比,这些药物可提高患者的生存率,并使治疗更具耐受性。然而,它们的使用与一系列对皮肤的毒性作用有关,包括滤泡脓疱,持续性炎症,干燥和瘙痒,以及对感染的敏感性增加。皮肤稳态的这种显着损害强调了EGFR-配体系统在整个皮肤免疫系统中的中心地位。迄今为止,尚无基于机制的方法可用于专门抵消抗EGFR药物或任何其他类别的酪氨酸激酶抑制剂的不利影响。只有了解人类这些不良反应背后的细胞和分子事件,再加上能够模拟这些毒性反应的体外/体内模型,才能指导基于机制的治疗或预防策略的发展。

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