Penn Epigenetics Institute, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA, USA.
Department of Dermatology, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA, USA.
Expert Opin Ther Targets. 2020 Jul;24(7):671-678. doi: 10.1080/14728222.2020.1762175. Epub 2020 May 7.
Cutaneous squamous cell carcinoma (cSCC) is the second most frequent cancer; it can be locally invasive and metastatic. cSCC is an immense clinical and economic problem given its sheer incidence and potential morbidity and mortality, particularly in the elderly and immunocompromised. Epigenetics has emerged as one of the most exciting areas of human biology, impacting virtually all areas of cellular physiology. Inhibition of an epigenetic enzyme is a potential treatment of cSCC.
We provide an overview of the development of inhibitors targeting the lysine demethylase, LSD1 (KDM1A), the first histone demethylase discovered. We summarize current treatment modalities for cSCC and provide a rationale for why epigenome-targeting therapies, and particularly LSD1 inhibitors, may be a novel and effective approach for treating pre-malignant and malignant cSCCs. A search was conducted in PubMed utilizing the combination of 'LSD1' with keywords such as 'epidermis,' 'squamous cell carcinoma,' or 'skin.' Relevant papers from 2000 to 2020 were reviewed.
Given the ability of LSD1 inhibitors to promote epidermal differentiation and enhance anti-tumor immune responses, LSD1 inhibitors may offer a highly effective therapeutic approach for the prevention and treatment of these ubiquitous cancers.
皮肤鳞状细胞癌（cSCC）是第二常见的癌症；它可以局部侵袭和转移。鉴于其发病率极高，以及老年人和免疫功能低下者的潜在发病率和死亡率，cSCC 是一个巨大的临床和经济问题。表观遗传学已成为人类生物学最令人兴奋的领域之一，几乎影响到细胞生理学的所有领域。抑制表观遗传酶是治疗 cSCC 的一种潜在方法。
我们概述了靶向赖氨酸去甲基酶 LSD1（KDM1A）的抑制剂的开发情况，LSD1 是最早发现的组蛋白去甲基酶。我们总结了目前治疗 cSCC 的方法，并提供了为什么表观基因组靶向治疗，特别是 LSD1 抑制剂，可能是治疗癌前和恶性 cSCC 的一种新颖而有效的方法的基本原理。在 PubMed 中使用“LSD1”与“表皮”、“鳞状细胞癌”或“皮肤”等关键字的组合进行了搜索。回顾了 2000 年至 2020 年的相关论文。
鉴于 LSD1 抑制剂能够促进表皮分化并增强抗肿瘤免疫反应，LSD1 抑制剂可能为预防和治疗这些普遍存在的癌症提供一种非常有效的治疗方法。
