# Telomerase Activity in Melanoma: Impact on Cancer Cell Proliferation Kinetics, Tumor Progression, and Clinical Therapeutic Strategies—A Scoping Review

## TL;DR

This review explores how telomerase activity in melanoma affects cancer cell growth and treatment, highlighting new strategies to target this enzyme.

## Contribution

The paper provides a comprehensive overview of telomerase's role in melanoma and outlines novel therapeutic approaches.

## Key findings

- Telomerase-related markers correlate with melanoma disease stage and patient survival.
- TERT promoter mutations are the most common noncoding alteration in melanoma.
- Telomerase-targeted therapies face challenges due to resistance and delayed cytotoxicity.

## Abstract

Melanoma treatment has improved greatly in recent years due to the development of many new cancer drugs. Many melanomas—50–82% of cases—carry changes in the telomerase reverse transcriptase (TERT) gene, which activates telomerase, an enzyme that maintains chromosome ends called telomeres. Normally, telomeres shorten as cells age; however, in melanoma, telomerase stays active, allowing cancer cells to keep dividing. Although telomerase clearly supports tumor growth, its role in how quickly melanoma cells multiply is not fully understood. This review summarizes current research showing that telomerase-related markers can predict disease severity. Scientists are developing telomerase-targeted drugs and immunotherapies, though resistance remains a challenge.

Background: Melanoma outcomes have improved in recent years as a result of modern systemic therapies. A major molecular feature of melanoma is abnormal telomerase activation; this is most often caused by telomerase reverse transcriptase (TERT) promoter mutations, which occur in 50–82% of cases and are the most common noncoding alteration in this cancer. Telomerase maintains telomere length, allowing melanoma cells to avoid senescence and continue dividing. However, how telomerase activity influences melanoma cell doubling time remains unclear, and the pathways linking TERT expression to faster cell-cycle progression require further study. Although telomerase inhibitors show promise in preclinical models, their clinical use is limited by delayed cytotoxicity and resistance. Materials and Methods: A scoping review was conducted using Scopus, ScienceDirect, MEDLINE/PubMed, and CINAHL (Cumulative Index to Nursing and Allied Health Literature). Keywords included “telomerase,” “melanoma,” “cancer,” “cell proliferation,” and “doubling time,” using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Telomerase-related biomarkers were found to correlate with disease stage and survival. Suggested therapeutic strategies include enzyme inhibitors, cytotoxic nucleotide incorporation, telomere destabilization, and immunotherapies such as peptide or dendritic cell vaccines, etc. Conclusions: Understanding both telomere-dependent and -independent TERT functions is essential for developing effective biomarkers and therapies that overcome resistance and slow melanoma progression.