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

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Preprints.org
DOI
10.20944/preprints202512.0695.v1

Melanoma survival has improved markedly in the past decade with new systemic agents. A key molecular hallmark is aberrant telomerase activation, largely driven by telomerase reverse transcriptase (TERT) promoter mutations (which are present in 50–82% of cases). These mutations represent the most frequent noncoding alteration in melanoma. Telomerase activation results in replicative immortality by maintaining telomere length, so cancer cells bypass senescence and apoptosis. However, the relationship between telomerase activity and melanoma cell population doubling time remains poorly defined. Pathways linking telomerase expression to accelerated cell cycle progression require further study. While telomerase inhibitors show preclinical promise, clinical application is limited by delayed cytotoxicity and resistance mechanisms. No review has yet mapped evidence connecting telomerase activity with melanoma proliferation kinetics and doubling time. 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.” The PRISMA framework guided our analysis of published studies. Results: Telomerase is clinically relevant for diagnosis, prognosis, and therapy. Biomarkers such as telomere length, telomerase activity, and TERRA expression correlate with disease stage and survival. Therapeutic strategies include enzyme inhibitors (e.g., Imetelstat), cytotoxic nucleotide incorporation, telomere destabilization, and immunotherapies such as peptide or dendritic cell vaccines, DNA vaccines, and CAR-T cells. Resistance often arises through alternative telomere maintenance mechanisms. Targeting extratelomeric TERT functions offers promise but remains complex. Conclusions: Telomerase drives melanoma progression through telomere-dependent and independent mechanisms, influencing proliferation, survival, metabolism, and genome stability. Clarifying these processes is essential for developing biomarkers and therapies that effectively target telomerase, overcome resistance, limit cancer progression and potentially provide another useful therapeutic option against melanoma.

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