Department of Biotechnology, Chemistry and Pharmacy, Department of Excellence 2018-2022, via Aldo Moro 2, I- 53100 Siena, University of Siena, Siena, Italy.
Department of Pharmacy, Department of Excellence 2018-2022, University of Napoli Federico II, via D. Montesano 49, I-80131 Napoli, Italy.
Curr Top Med Chem. 2020;20(6):433-457. doi: 10.2174/1568026620666200102104930.
Telomeres are protective chromosomal ends that shield the chromosomes from DNA damage, exonucleolytic degradation, recombination, and end-to-end fusion. Telomerase is a ribonucleoprotein that adds TTAGGG tandem repeats to the telomeric ends. It has been observed that 85 to 90% of human tumors express high levels of telomerase, playing a crucial role in the development of cancers. Interestingly, the telomerase activity is generally absent in normal somatic cells. This selective telomerase expression has driven scientists to develop novel anti-cancer therapeutics with high specificity and potency. Several advancements have been made in this area, which is reflected by the enormous success of the anticancer agent Imetelstat. Since the discovery of Imetelstat, several research groups have contributed to enrich the therapeutic arsenal against cancer. Such contributions include the application of new classes of small molecules, peptides, and hTERT-based immunotherapeutic agents (p540, GV1001, GRNVAC1 or combinations of these such as Vx-001). Many of these therapeutic tools are under different stages of clinical trials and have shown promising outcomes. In this review, we highlight the current status of telomerase-based cancer therapeutics and the outcome of these investigations.
端粒是保护性染色体末端，可防止染色体受到 DNA 损伤、核酸外切酶降解、重组和端到端融合的影响。端粒酶是一种核糖核蛋白，可将 TTAGGG 串联重复序列添加到端粒末端。已经观察到，85%至 90%的人类肿瘤表达高水平的端粒酶，在癌症的发展中起着关键作用。有趣的是，端粒酶活性通常不存在于正常体细胞中。这种选择性的端粒酶表达促使科学家开发出具有高特异性和效力的新型抗癌治疗方法。在这一领域已经取得了一些进展，抗癌药物 Imetelstat 的巨大成功就反映了这一点。自 Imetelstat 发现以来，几个研究小组已经为丰富抗癌治疗武器库做出了贡献。这些贡献包括应用新类别的小分子、肽和基于 hTERT 的免疫治疗剂（p540、GV1001、GRNVAC1 或这些药物的组合，如 Vx-001）。这些治疗工具中的许多都处于不同的临床试验阶段，并显示出了有前景的结果。在这篇综述中，我们强调了基于端粒酶的癌症治疗方法的现状以及这些研究的结果。
