Brain Tumor & Telomerase reverse transcriptase (TERT) скачать в хорошем качестве

Brain Tumor & Telomerase reverse transcriptase (TERT)

Telomerase reverse transcriptase (TERT) serves as the rate-limiting catalytic subunit of telomerase, a critical enzyme that allows malignant cells to achieve replicative immortality by synthesizing telomeric repeats to overcome the progressive shortening of chromosome ends. Beyond this canonical role, evidence highlights TERT's extratelomeric functions, where it acts as a transcriptional co-regulator for survival pathways such as NF-κB, Wnt/β-catenin, and MYC, while also supporting mitochondrial homeostasis and resistance to apoptosis. Highly recurrent somatic promoter mutations (C228T and C250T) are fundamental drivers of TERT reactivation, appearing with remarkable frequency in melanoma (71%), glioblastoma (83%), and urothelial carcinoma (66%). These mutations, alongside epigenetic mechanisms like THOR hypermethylation, serve as robust biomarkers for aggressive tumor behavior and poor clinical outcomes across multiple organ systems. Consequently, the clinical landscape is increasingly focused on TERT-targeted interventions, including direct enzymatic inhibitors like Imetelstat, therapeutic vaccines such as UV1 and GV1001, and stalled-complex nucleosides like 6-thio-dG, which offer the potential to rapidly disrupt telomere maintenance and overcome resistance in refractory malignancies. While challenges like hematologic toxicity and the emergence of the alternative lengthening of telomeres (ALT) pathway persist, these advances represent a multifaceted approach to dismantling one of cancer's core survival mechanisms.