Oligonucleotides and microRNAs Targeting Telomerase Subunits in Cancer Therapy

Area of Science:

• Oncology
• Molecular Biology
• Biotechnology

Background:

• Telomerase overexpression is a hallmark of cancer, granting cells replicative immortality.
• Targeting telomerase offers a promising alternative to conventional cancer therapies like chemotherapy and radiotherapy.
• Oligonucleotide-based therapies represent a unique and diverse class of telomerase inhibitors with clinical potential.

Purpose of the Study:

• To review the conceptual basis and current status of oligonucleotide-based therapeutics targeting telomerase subunits.
• To explore the advantages and disadvantages of various oligonucleotide approaches for cancer treatment.
• To highlight the role of microRNAs and antisense oligonucleotides in modulating telomerase activity.

Main Methods:

• Review of preclinical and clinical studies on oligonucleotide-based telomerase inhibitors.
• Analysis of microRNA-based strategies targeting hTERT expression.
• Evaluation of antisense oligonucleotides (e.g., GRN163L, T-oligos) and G-quadruplex stabilizers (e.g., Telomestatin).

Main Results:

• MicroRNAs (tumor suppressors like miRNA-512-5p and oncogenic like miRNA-19b) show preclinical promise in targeting hTERT.
• Antisense oligonucleotides effectively target telomerase subunits, advancing novel cancer therapy design.
• G-quadruplex stabilizers inhibit telomerase by preserving telomeric structure, preventing hTERC binding.

Conclusions:

• Oligonucleotide-based strategies targeting telomerase subunits (hTERT, hTERC) are a developing area in cancer therapeutics.
• MicroRNAs and antisense oligonucleotides offer distinct mechanisms for telomerase inhibition.
• Further research into these approaches, including their benefits and limitations, is warranted for clinical application.