Managing telomerase and telomere dysfunction in acral melanoma

Abstract

Acral Lentiginous Melanoma is a rare and aggressive subtype of melanoma that commonly affects the palms, soles, and nail beds. It is more prevalent in individuals with darker skin tones, including Asian, African, and Hispanic populations. Unlike cutaneous melanomas, acral melanoma is not associated with UV exposure and has a distinct genetic and molecular profile, underscoring the need for tailored research and treatment strategies. Standard treatments, such as surgery, chemotherapy, immunotherapy, and targeted therapies, have shown limited success for this melanoma subtype, highlighting the urgency of developing more effective interventions. Telomerase is an enzyme that extends telomeres and is a key target in acral melanoma which exhibits’ high telomerase activity, driven by mutations in the telomerase reverse transcriptase TERT promoter, which contributes to uncontrolled tumor cell proliferation, cancer cell immortality, and resistance to conventional therapies. Therefore, targeting telomerase presents a promising therapeutic avenue for acral melanoma patients who do not respond well to current treatments. Several approaches for targeting telomerase deregulation have been developed, and their potential for the management of acral melanoma is discussed in this review. Specifically, the promise of telomerase-targeted therapies for acral melanoma is emphasized and explores how these strategies could improve outcomes for patients with this challenging skin cancer. By focusing on the role of telomerase in tumorigenesis and treatment resistance, telomerase-targeted strategies hold potential as a foundational component of therapies for acral melanoma, complementing existing approaches.