摘要
非黑色素瘤皮肤癌是人类最常见的恶性肿瘤,在免疫功能正常的患者中,其与基底/鳞状细胞癌的发病率的比例为4:1。基底细胞癌很少转移但会引起明显的局部组织破坏和缺陷,而鳞状细胞癌是一种高风险的与复发性和转移性有关的疾病。转移性癌症患者预后较差。如果根据原发肿瘤的特点和患者的情况适当地治疗,治愈率可以大于90%。但在特定的情况下,用 5-氟尿嘧啶、咪喹莫特、双氯芬酸和ingenol mebutate进行治疗,可以提供了一个很好的治愈机会,通常有极好的治疗效果。在晚期和转移性非黑素瘤皮肤癌的情况下,新开发的分子靶向治疗是替代经典细胞抑制剂的很好的选择。特别是,单克隆抗体cetuximab针对抑制表皮生长因子受体,其在鳞状细胞癌患者有效性和耐受性较好。最近关于基底细胞癌患者Hedgeho信号通路中突变方面的新发现促进了Hedgehog信号通路抑制剂vismodegib的研究进展,这也是最近被批准用于局部晚期或转移性基底细胞癌治疗的方法。本文对参与NMSC发病的分子途径进行了全面的概述,并主要关注于其作用机理、适应症、疗效、副作用和专门针对这些途径的分子靶标的新疗法的禁忌症。
关键词: 基底细胞癌,表皮细胞信号转导通路,鳞状细胞癌,靶向治疗。
Current Drug Targets
Title:New Perspectives in the Pharmacological Treatment of Non-Melanoma Skin Cancer
Volume: 17 Issue: 3
Author(s): Paola Savoia, Ottavio Cremona and Paolo Fava
Affiliation:
关键词: 基底细胞癌,表皮细胞信号转导通路,鳞状细胞癌,靶向治疗。
摘要: Non-melanoma skin cancers are the most common malignancy in humans, with a basal/squamous cell carcinoma incidence ratio of 4:1 in immunocompetent patients. Basal cell carcinoma rarely metastasizes but commonly causes significant local tissue destruction and disfigurement, whereas squamous cell carcinoma is associated with a substantial risk of recurrence and metastasis; the prognosis in metastatic patients is poor. Surgical approaches give a cure rate greater than 90% if appropriately applied, on the basis of the characteristics of the primary tumors and of the patients, but in selected cases, medical treatment (5-fluorouracil, imiquimod, diclofenac and, more recently, ingenol mebutate) is preferable to invasive procedures and provides a good chance of cure, with generally excellent cosmetic outcomes. In case of advanced and metastatic non-melanoma skin cancer, newly developed molecularly targeted therapy represents a reasonably promising alternative to classical cytostatics. In particular, the monoclonal antibody cetuximab, directed against the epidermal growth factor receptor, is effective and well-tolerated in squamous cell carcinoma patients. Moreover, the recent identification of mutations in the Hedgehog signaling pathway in basal cell carcinoma lead to the development of the smoothened Hedgehog pathway inhibitor vismodegib, that was recently approved for the treatment of locally advanced or metastatic basal cell carcinoma. In this review we provide an overview of the molecular pathways involved in NMSC pathogenesis, focusing on the mechanisms of action, indications, efficacy, side effects and contraindications of new medical treatments that specifically tackle molecular targets of these pathways.
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Paola Savoia, Ottavio Cremona and Paolo Fava , New Perspectives in the Pharmacological Treatment of Non-Melanoma Skin Cancer, Current Drug Targets 2016; 17 (3) . https://dx.doi.org/10.2174/1389450116666150806123717
DOI https://dx.doi.org/10.2174/1389450116666150806123717 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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