Telomerase as a therapeutic target in glioblastoma

被引：32

作者：

Aquilanti, Elise ^{[1
,2
]}

Kageler, Lauren ^{[2
]}

Wen, Patrick Y. ^{[1
]}

Meyerson, Matthew ^{[2
,3
,4
]}

机构：

[1] Dana Farber Canc Inst, Div Neuro Oncol, Boston, MA 02115 USA

[2] Broad Inst, Canc Program, Cambridge, MA USA

[3] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA

[4] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA

来源：

NEURO-ONCOLOGY | 2021年 / 23卷 / 12期

关键词：

genomic driver; glioblastoma; targeted therapies; telomerase; TERT PROMOTER MUTATIONS; REVERSE-TRANSCRIPTASE; INHIBITOR IMETELSTAT; CATALYTIC SUBUNIT; PHASE-II; CANCER; HETEROGENEITY; RECURRENT; CELLS; GRN163L;

D O I：

10.1093/neuonc/noab203

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Glioblastoma is the most common primary malignant brain tumor in adults and it continues to have a dismal prognosis. The development of targeted therapeutics has been particularly challenging, in part due to a limited number of oncogenic mutations and significant intra-tumoral heterogeneity. TERT promoter mutations were first discovered in melanoma and later found to be present in up to 80% of glioblastoma samples. They are also frequent clonal alterations in this tumor. TERT promoter mutations are one of the mechanisms for telomerase reactivation, providing cancers with cellular immortality. Telomerase is a reverse transcriptase ribonucleoprotein complex that maintains telomere length in cells with high proliferative ability. In this article, we present genomic and pre-clinical data that support telomerase as a potential "Achilles' heel" for glioblastoma. We also summarize prior experience with anti-telomerase agents and potential new approaches to tackle this target.

引用

页码：2004 / 2013

页数：10

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