将旧概念与新概念结合在靶向端粒酶治疗癌症方面：短暂、即时、完全和综合攻击（TICCA）
Combining old and new concepts in targeting telomerase for cancer therapy: transient, immediate, complete and combinatory attack (TICCA).
发表日期：2023 Sep 07
作者：
Jaber Haj Ali, Michael Walter
来源：
Cellular & Molecular Immunology
摘要：
端粒酶通过延长端粒的长度来克服复制衰老，但也是大多数癌细胞中的一个特定元素。它的表达比其他任何肿瘤标志物都要广泛。作为诱导复制无限生命周期的肿瘤靶点，端粒酶只能被另一种机制——端粒长度的替代（ALT）所克服。这限制了发展耐药性的可能性。此外，端粒酶抑制在正常细胞中具有较低的毒性风险，具有一定程度的专一性。然而，目前只有一种端粒酶拮抗剂进入了后期临床研究。本综述总结了端粒酶基于最新技术进展的潜在原因、治疗陷阱和未来机会。基于新的发现和方法，我们提出了一个概念，可以显著改善端粒酶基因治疗中的长期生存：TICCA（Transient Immediate Complete and Combinatory Attack）策略。© 2023. BioMed Central Ltd., part of Springer Nature.
Telomerase can overcome replicative senescence by elongation of telomeres but is also a specific element in most cancer cells. It is expressed more vastly than any other tumor marker. Telomerase as a tumor target inducing replicative immortality can be overcome by only one other mechanism: alternative lengthening of telomeres (ALT). This limits the probability to develop resistance to treatments. Moreover, telomerase inhibition offers some degree of specificity with a low risk of toxicity in normal cells. Nevertheless, only one telomerase antagonist reached late preclinical studies. The underlying causes, the pitfalls of telomerase-based therapies, and future chances based on recent technical advancements are summarized in this review. Based on new findings and approaches, we propose a concept how long-term survival in telomerase-based cancer therapies can be significantly improved: the TICCA (Transient Immediate Complete and Combinatory Attack) strategy.© 2023. BioMed Central Ltd., part of Springer Nature.