Abstract 6888: Targeting melanoma cells through G-quadruplex formation: mechanism and enhanced efficacy of T-oligo in combination therapy

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Abstract Melanoma is one of the deadliest skin cancers in the world, estimated to cause 7, 990 deaths annually. Telomerase binds to the 3' overhang of the telomere, causing telomere elongation and cell survival. Treatment against melanoma aims at targeting the 3' telomere overhang using T-oligo, which is a guanine-rich oligonucleotide homologous to the telomere overhang, preventing the growth of melanoma cells by inducing apoptosis. As a guanine-rich oligonucleotide, T-oligo can form G-quadruplexes (G4), secondary structures of nucleic acids, which we aim to detect using FRET microscopy in melanoma cells. Currently, vemurafenib and trametinib are agents that are used to treat melanoma. We were also interested in studying the combinational treatment of T-oligo with vemurafenib/trametinib to determine if it improves the efficacy of these drugs as compared to monotherapy in melanoma cells. We hypothesize that T-oligo forms G-quadruplexes in the nucleus of melanoma cells, and combination therapy of vemurafenib/Trametinib with T-oligo would be efficacious compared to monotherapy. Citation Format: Rose Bahari, Stephanie M. Lopez, Archit Agnihotri, Hyatt Alaraj, Lawrence Miller, Neelu Puri. Targeting melanoma cells through G-quadruplex formation: mechanism and enhanced efficacy of T-oligo in combination therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6888.

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