Bollu Vishnu Sravan, Chen Yu-Chi, Zhang Fan, Gowda Krishne, Amin Shantu, Sharma Arun K, Schell Todd D, Zhu Jiyue, Robertson Gavin P
Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA 17033, United States; Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA 17033, United States.
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA 17033, United States; Department of Pharmaceutical Sciences, Washington State University College of Pharmacy and Pharmaceutical Sciences, Spokane, WA 99202, United States.
Pharmacol Res. 2025 May;215:107700. doi: 10.1016/j.phrs.2025.107700. Epub 2025 Mar 15.
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.
肢端雀斑样痣黑色素瘤是一种罕见且侵袭性强的黑色素瘤亚型，通常累及手掌、足底和甲床。它在肤色较深的个体中更为常见，包括亚洲、非洲和西班牙裔人群。与皮肤黑色素瘤不同，肢端黑色素瘤与紫外线暴露无关，具有独特的基因和分子特征，这凸显了制定针对性研究和治疗策略的必要性。手术、化疗、免疫疗法和靶向疗法等标准治疗方法对这种黑色素瘤亚型的疗效有限，这突出了开发更有效干预措施的紧迫性。端粒酶是一种延长端粒的酶，是肢端黑色素瘤的关键靶点，该酶表现出高活性，由端粒酶逆转录酶TERT启动子的突变驱动，这导致肿瘤细胞不受控制地增殖、癌细胞永生以及对传统疗法产生抗性。因此，针对端粒酶为对当前治疗反应不佳的肢端黑色素瘤患者提供了一条有前景的治疗途径。已经开发了几种针对端粒酶失调的方法，本综述讨论了它们在肢端黑色素瘤治疗中的潜力。具体而言，强调了端粒酶靶向疗法对肢端黑色素瘤的前景，并探讨了这些策略如何改善这种具有挑战性的皮肤癌患者的治疗结果。通过关注端粒酶在肿瘤发生和治疗抗性中的作用，端粒酶靶向策略有望成为肢端黑色素瘤治疗的基础组成部分，补充现有方法。
