When the Ends Are Really the Beginnings: Targeting Telomerase for Treatment of GBM

Abstract

Purpose of review: High-throughput genomic sequencing has identified alterations in the gene encoding human telomerase reverse transcriptase (TERT) as points of interest for elucidating the oncogenic mechanism of multiple different cancer types, including gliomas. In gliomas, the TERT promoter mutation (TPM) and resultant overexpression of TERT are observed mainly in the most aggressive (primary glioblastoma/grade IV astrocytoma) and the least aggressive (grade II oligodendroglioma) cases. This article reviews recent research on (1) the mechanism of TERT activation in glioma, (2) downstream consequences of TERT overexpression on glioma pathogenesis, and (3) targeting TPMs as a therapeutic strategy.

Recent findings: New molecular classifications for gliomas include using TPMs, where the mutant group demonstrates the worst prognosis. Though a canonical function of TERT is established in regard to telomere maintenance, recent studies on non-canonical functions of TERT explore varied roles of telomerase in tumor progression and maintenance. Somatic alterations of the TERT promoter present a promising target for novel therapeutics development in primary glioma treatment.

Keywords: Cellular functions of TERT; GBM; Glioblastoma; TERT promoter mutation (TPM); Telomerase reverse transcriptase (TERT); Therapeutic targeting of TERT.