Abstract 7201: Targeting TAZ-TEAD in minimal residual disease enhances the duration of targeted therapy in melanoma models

Abstract Targeted therapies in cancer are limited by drug tolerance. In melanoma, tolerance to MAPK pathway inhibitors is associated with loss of SOX10 and enhanced YAP1/TAZ-TEAD activity. We show that loss of SOX10 is sufficient to up-regulate a TEAD transcriptional program with a strong dependence on TAZ. We developed a unique gene signature based on the transcriptomic changes following TAZ or YAP1 depletion. Expression of active TAZ was sufficient to mediate tolerance to BRAF inhibitors and MEK inhibitors. In WM983B cells, depletion of TAZ significantly reduced cell growth, whereas YAP1 knockdown resulted in little to no effect. These studies demonstrate that TAZ-TEAD activity plays an important role in melanoma drug tolerance and the development of acquired resistance. Citation Format: Connor A. Ott, Timothy Purwin, Manoela Tiago, Kristine Lou, Pan-Yu Chen, Somaneth Chowdhury, Glenn Mersky, Nir Hacohen, John Lamar, Claudia Capparelli, Gideon Bollag, Andrew Aplin. Targeting TAZ-TEAD in minimal residual disease enhances the duration of targeted therapy in melanoma models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7201.