Telomerase in cancer- ongoing quest and future discoveries

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Telomerase, comprising telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC), is usually repressed in differentiated human cells.
• Dysregulation of telomerase contributes to cancer via telomere-dependent and independent pathways, with elevated activity in advanced cancers.
• TERT and TERC have roles beyond telomere maintenance, influencing gene expression, signaling, and metabolism.

Purpose of the Study:

• To review the multifaceted roles of telomerase in cancer development and progression.
• To explore the non-canonical functions of TERT, including its nuclear and mitochondrial roles.
• To discuss therapeutic strategies targeting telomerase and TERT in cancer treatment.

Main Methods:

• Literature review of studies on telomerase, TERT, and TERC in cancer.
• Analysis of telomerase's roles in gene expression, cellular metabolism, and DNA protection.
• Exploration of oncogenic virus strategies to manipulate telomerase activity.
• Review of current and emerging telomerase-targeted cancer therapies.
• Consideration of computational modeling applications in telomere research.

Main Results:

• TERT reactivation and TERC upregulation are observed in early tumorigenesis.
• TERT's presence in nucleus and mitochondria highlights non-canonical functions, preventing cell death and protecting mitochondrial DNA.
• Telomerase activity is linked to altered glucose metabolism and epigenetic regulation in cancer cells.
• Oncogenic viruses utilize strategies to enhance telomerase activity for cancer progression.
• Telomerase inhibitors, nutraceuticals, and vaccines are promising therapeutic avenues.

Conclusions:

• Telomerase, particularly TERT, plays pivotal roles in cancer initiation and progression.
• Understanding telomerase activation mechanisms is crucial for developing effective targeted therapies.
• Computational modeling offers potential for novel insights into telomere research and therapy development.