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西米普利单抗与皮肤鳞状细胞癌:从实验室到临床

Cemiplimab and Cutaneous Squamous Cell Carcinoma: From Bench to Bedside.

作者信息

Goodman D T

机构信息

Department of Plastic Surgery, Cork University Hospital, Wilton, Co Cork, Ireland.

出版信息

JPRAS Open. 2022 Jun 23;33:155-160. doi: 10.1016/j.jpra.2022.06.003. eCollection 2022 Sep.

Abstract

Non-melanoma skin cancers (NMSCs) are the most common cancer in fair-skinned individuals with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) being the most common subtype. While BCC has historically been the most common NMSC, SCC is increasing in incidence relative to BCC. SCC has a very poor prognosis with advanced local infiltration or when it achieves a metastatic state with around 50% of patients with locally advanced disease relapsing with an average overall survival of 10-13 months for patients with recurrent or metastatic disease. The pathogenesis of cutaneous SCC (cSCC) is multifactorial, and many studies have also described in detail the strong link between tumour apoptosis, DNA repair mechanism deficiencies, and developing cSCC. Patients with TP53 mutations are more susceptible to develop cSCC, thus highlighting the importance of cell cycle regulation and also pointing towards the potential therapeutic targets within. This review illustrates the role of the programmed death receptor-1 (PD-1) inhibitor cemiplimab in treating advanced and metastatic cSCC not suitable to surgical excision and describes its development in the context of the translational research paradigm from preclinical studies to its licenced implementation in clinical care and beyond.

摘要

非黑色素瘤皮肤癌(NMSCs)是白皮肤个体中最常见的癌症,基底细胞癌(BCC)和鳞状细胞癌(SCC)是最常见的亚型。虽然BCC历来是最常见的NMSC,但SCC的发病率相对于BCC正在上升。SCC的预后非常差,出现局部浸润进展或发生转移时,约50%的局部晚期疾病患者会复发,复发或转移性疾病患者的平均总生存期为10 - 13个月。皮肤鳞状细胞癌(cSCC)的发病机制是多因素的,许多研究也详细描述了肿瘤细胞凋亡、DNA修复机制缺陷与cSCC发生之间的紧密联系。TP53基因突变的患者更易发生cSCC,这凸显了细胞周期调控的重要性,也指出了其中潜在的治疗靶点。本综述阐述了程序性死亡受体1(PD - 1)抑制剂西米普利单抗在治疗不适于手术切除的晚期和转移性cSCC中的作用,并描述了其在从临床前研究到临床护理及其他方面的转化研究范式背景下的发展历程。

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