Ramchatesingh Brandon, Gantchev Jennifer, Villarreal Amelia Martínez, Gill Raman Preet Kaur, Lambert Marine, Sivachandran Sriraam, Lefrançois Philippe, Litvinov Ivan V
Division of Experimental Medicine, McGill University, Montreal, QC H4A 3J1, Canada.
Cancer Research Program, Research Institute of the McGill University Health Center, Montreal, QC H4A 3J1, Canada.
Cancers (Basel). 2022 Jul 26;14(15):3630. doi: 10.3390/cancers14153630.
Keratinocyte carcinomas are among the most prevalent malignancies worldwide. Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the two cancers recognized as keratinocyte carcinomas. The standard of care for treating these cancers includes surgery and ablative therapies. However, in recent years, targeted therapies (e.g., cetuximab for cSCC and vismodegib/sonidegib for BCC) have been used to treat advanced disease as well as immunotherapy (e.g., cemiplimab). These treatments are expensive and have significant toxicities with objective response rates approaching ~50-65%. Hence, there is a need to dissect the molecular pathogenesis of these cancers to identify novel biomarkers and therapeutic targets to improve disease management. Several cancer-testis antigens (CTA) and developmental genes (including embryonic stem cell factors and fetal genes) are ectopically expressed in BCC and cSCC. When ectopically expressed in malignant tissues, functions of these genes may be recaptured to promote tumorigenesis. CTAs and developmental genes are emerging as important players in the pathogenesis of BCC and cSCC, positioning themselves as attractive candidate biomarkers and therapeutic targets requiring rigorous testing. Herein, we review the current research and offer perspectives on the contributions of CTAs and developmental genes to the pathogenesis of keratinocyte carcinomas.
角质形成细胞癌是全球最常见的恶性肿瘤之一。基底细胞癌（BCC）和皮肤鳞状细胞癌（cSCC）是被认可的两种角质形成细胞癌。治疗这些癌症的标准护理方法包括手术和消融疗法。然而，近年来，靶向疗法（如用于cSCC的西妥昔单抗和用于BCC的维莫德吉/索尼德吉）以及免疫疗法（如西米普利单抗）已被用于治疗晚期疾病。这些治疗费用高昂且具有显著毒性，客观缓解率约为50%-65%。因此，有必要剖析这些癌症的分子发病机制，以确定新的生物标志物和治疗靶点，从而改善疾病管理。几种癌-睾丸抗原（CTA）和发育基因（包括胚胎干细胞因子和胎儿基因）在BCC和cSCC中异位表达。当在恶性组织中异位表达时，这些基因的功能可能会被重新激活以促进肿瘤发生。CTA和发育基因正在成为BCC和cSCC发病机制中的重要参与者，使其成为需要严格测试的有吸引力的候选生物标志物和治疗靶点。在此，我们综述了当前的研究，并就CTA和发育基因对角质形成细胞癌发病机制的贡献提供了观点。
