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针对结质母细胞瘤的端粒酶向疗法的进展:系统性审查

Giovanni Pennisi^1,2, Placido Bruzzaniti^2,3, Benedetta Burattini¹

¹Department of Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.

International journal of molecular sciences

|August 29, 2024

概括

针对质母细胞瘤 (GBM) 的端粒酶向显示出希望,但面临挑战. 由于复杂的监管和药物输送不良,目前的治疗方法在很大程度上没有成功,需要像疫苗这样的新策略.

科学领域:

神经瘤学神经瘤学
分子生物学分子生物学
癌症治疗方法癌症治疗方法

背景情况:

质母细胞瘤 (GBM) 是一种具有不良预后和有限治疗选择的侵袭性脑瘤.
人类端粒酶逆转录酶 (hTERT) 促进子突变在GBM中很常见,使得端粒酶成为关键的治疗标.
目前标准的GBM治疗方法在十年多的时间里几乎没有得到改善.

研究的目的:

审查GBM中端粒酶的生物学.
探索针对GBM的端粒酶向疗法的疗效和挑战.
确定GBM的未来治疗策略.

主要方法:

从MEDLINE/PubMed和Scopus (1995-2024) 中对文学进行系统审查.
搜索术语包括"GBM"",高度质瘤"",hTERT"和"端粒酶".
在GBM中包括36项研究,重点是以端粒酶为向的疗法,不包括评论和非英语文章.

主要成果:

对hTERT抑制剂的临床前研究显示有希望,但由于复杂的调节和药理动力学,临床试验失败了.
直接端粒酶抑制剂面临诸如缓慢的端粒缩短和替代端粒延长 (ALT) 的激活等障碍.
经过测试的端粒酶抑制剂Imetelstat在GBM中具有有限的疗效,尽管在其他癌症中取得了成功.

结论:

针对GBM的端粒酶向治疗是具有挑战性的,因为复杂的hTERT调节和不充分的药物输送.
目前没有批准用于GBM的端粒酶抑制剂,临床试验取得了有限的成功.
未来的策略可能包括基于端粒酶的疫苗和多位抑制剂,以改善GBM治疗结果.

关键词:

大脑瘤是个大脑瘤质母细胞瘤 (GBM) 是一种 hTERT 抑制剂的使用多位抑制剂多位抑制剂以端粒酶为向的治疗方法.

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