Abstract:
Head and neck cancers (HNCs) are among the ten leading malignancies worldwide. Despite significant progress in all therapeutic modalities, predictive biomarkers, and targeted therapies for HNCs are limited and the survival rate is unsatisfactory. The importance of telomere maintenance via telomerase reactivation in carcinogenesis has been demonstrated in recent decades. Several mechanisms could activate telomerase reverse transcriptase (TERT), the most common of which is promoter alternation. Two major hotspot TERT promoter mutations (C228T and C250T) have been reported in different malignancies such as melanoma, genitourinary cancers, CNS tumors, hepatocellular carcinoma, thyroid cancers, sarcomas, and HNCs. The frequencies of TERT promoter mutations vary widely across tumors and is quite high in HNCs (11.9-64.7%). These mutations have been reported to be more enriched in oral cavity SCCs and HPV-negative tumors. The association between TERT promoter mutations and poor survival has also been demonstrated. Till now, several therapeutic strategies targeting telomerase have been developed although only a few drugs have been used in clinical trials. Here, we briefly review and summarize our current understanding and evidence of TERT promoter mutations in HNC patients.
摘要:
头颈癌(HNC)是全球十大恶性肿瘤之一。尽管在所有治疗方式上都取得了重大进展,预测性生物标志物,和HNC的靶向治疗是有限的,生存率不令人满意。近几十年来,通过端粒酶再激活维持端粒在癌变中的重要性已得到证实。几种机制可以激活端粒酶逆转录酶(TERT),其中最常见的是启动子交替。两种主要热点TERT启动子突变(C228T和C250T)已被报道在不同的恶性肿瘤,如黑色素瘤,泌尿生殖系统癌症,中枢神经系统肿瘤,肝细胞癌,甲状腺癌,肉瘤,和HNC。TERT启动子突变的频率在肿瘤中差异很大,并且在HNC中相当高(11.9-64.7%)。据报道,这些突变在口腔SCC和HPV阴性肿瘤中更为丰富。TERT启动子突变与低存活率之间的关联也已被证明。到现在为止,尽管只有少数药物被用于临床试验,但已经开发了几种靶向端粒酶的治疗策略.这里,我们简要回顾并总结了我们目前对HNC患者TERT启动子突变的理解和证据.