Dysregulation of Epidermal Growth Factor Receptor in Actinic Keratosis and Squamous Cell Carcinoma
Dysregulation of Epidermal Growth Factor Receptor in Actinic Keratosis and Squamous Cell Carcinoma
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DOI：
10.1159/000367959
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发表时间：
2015-01-01
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影响因子：
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通讯作者：
Simpson, Fiona
中科院分区：
文献类型：
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作者：
Joseph, Shannon R.;Endo-Munoz, Liliana;Simpson, Fiona
表皮生长因子受体（EGFR）是一种受体酪氨酸激酶。其正确的功能是正常皮肤发育和体内平衡所必需的，而EGFR信号传导的失调导致细胞过度增殖和分化缺陷，导致伤口愈合受损、银屑病样病变的发展、毛囊的结构和功能缺陷以及肿瘤发生。光化性角化病，也称为日光性角化病，发生在皮肤的阳光暴露区域。这些通常被称为“癌前病变”，据说是原位早期鳞状细胞癌（SCC）的代表，尽管对其分类的争论仍在继续。抗EGFR疗法已被批准用于治疗几种恶性肿瘤，并正在对其他恶性肿瘤进行试验[1]，包括晚期皮肤鳞状细胞癌（CSCC）。然而，关于用抗EGFR抑制剂治疗CSCC仍存在许多问题。与其他类型的肿瘤（如头颈部SCC（HNSCC））相比，较少数量的CSCC肿瘤为EGFR阳性，并且已建议应基于高肿瘤EGFR表达选择患者。然而，有报告称，肿瘤患者对抗EGFR治疗无EGFR阳性染色反应。EGFR是许多肿瘤中的致癌驱动因素。它是否驱动光化性角化病转化为致瘤表型？许多这样的问题仍然存在，在这里，我们讨论表皮生长因子受体在SCC中的作用及其在皮肤癌发展的不同阶段的功能。(C)2015 S. Karger AG，巴塞尔
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase. Its correct function is required for normal skin development and homeostasis, while dysregulation of EGFR signalling results in cellular hyper-proliferation and defects in differentiation, leading to impaired wound healing, the development of psoriasis-like lesions, structural and functional defects of hair follicles and tumourigenesis. Actinic keratosis, which is also known as solar keratosis, develops in sun-exposed areas of the skin. These are often called 'premalignant lesions' and are said to represent early squamous cell carcinoma (SCC) in situ, although debate over their classification continues. Anti-EGFR therapies have been approved for the treatment of several malignancies and are undergoing trials for others [1], including advanced cutaneous squamous cell carcinoma (CSCC). However, a number of questions remain regarding the treatment of CSCC with anti-EGFR inhibitors. A lower number of CSCC tumours are EGFR positive in comparison to other types of tumours, such as head and neck SCC (HNSCC), and it has been suggested that patients should be selected on the basis of high tumour EGFR expression. However, there are reports of patients with tumours showing no EGFR-positive staining responding to anti-EGFR therapy. EGFR is an oncogenic driver in many tumours. Does it drive the transformation of actinic keratosis to a tumourigenic phenotype? Many such questions remain, and here, we discuss the role of EGFR in SCC and its functions during the different stages of skin cancer development. (C) 2015 S. Karger AG, Basel