biostudies-literatureKanai RMIT Ludwig Center for Molecular OncologyAlbany Medical College Dean’s Office Bridge GrantNIH Tumor Microenvironment NetworkNational Institutes of Health (NIH) National Research Service AwardHoward Hughes Medical InstituteNCIKoch Institute Frontier Research FundNCI NIH HHSDepartment of DefenseNIH HHS852https://www.ebi.ac.uk/biostudies/studies/S-EPMC10930532biostudies-literatureUnknown16(5)Targeted therapies are effective cancer treatments when accompanied by accurate diagnostic tests that can help identify patients that will respond to those therapies. The YAP/TAZ-TEAD axis is activated and plays a causal role in several cancer types, and TEAD inhibitors are currently in early-phase clinical trials in cancer patients. However, a lack of a reliable way to identify tumors with YAP/TAZ-TEAD activation for most cancer types makes it difficult to determine which tumors will be susceptible to TEAD inhibitors. Here, we used a combination of RNA-seq and bioinformatic analysis of metastatic melanoma cells to develop a YAP/TAZ gene signature. We found that the genes in this signature are TEAD-dependent in several melanoma cell lines, and that their expression strongly correlates with YAP/TAZ activation in human melanomas. Using DepMap dependency data, we found that this YAP/TAZ signature was predictive of melanoma cell dependence upon YAP/TAZ or TEADs. Importantly, this was not limited to melanoma because this signature was also predictive when tested on a panel of over 1000 cancer cell lines representing numerous distinct cancer types. Our results suggest that YAP/TAZ gene signatures like ours may be effective tools to predict tumor cell dependence upon YAP/TAZ-TEAD, and thus potentially provide a means to identify patients likely to benefit from TEAD inhibitors.CancersIdentification of a Gene Signature That Predicts Dependence upon YAP/TAZ-TEAD.PMC10930532U54CA163109W81XWH-14-1-0240CA1421442N.A.U54 CA163109U54 CA112967U54CA112967Kanai RNorton ELamar JMStern PHynes ROfalseIdentification of a Gene Signature That Predicts Dependence upon YAP/TAZ-TEAD.Targeted therapies are effective cancer treatments when accompanied by accurate diagnostic tests that can help identify patients that will respond to those therapies. The YAP/TAZ-TEAD axis is activated and plays a causal role in several cancer types, and TEAD inhibitors are currently in early-phase clinical trials in cancer patients. However, a lack of a reliable way to identify tumors with YAP/TAZ-TEAD activation for most cancer types makes it difficult to determine which tumors will be susceptible to TEAD inhibitors. Here, we used a combination of RNA-seq and bioinformatic analysis of metastatic melanoma cells to develop a YAP/TAZ gene signature. We found that the genes in this signature are TEAD-dependent in several melanoma cell lines, and that their expression strongly correlates with YAP/TAZ activation in human melanomas. Using DepMap dependency data, we found that this YAP/TAZ signature was predictive of melanoma cell dependence upon YAP/TAZ or TEADs. Importantly, this was not limited to melanoma because this signature was also predictive when tested on a panel of over 1000 cancer cell lines representing numerous distinct cancer types. Our results suggest that YAP/TAZ gene signatures like ours may be effective tools to predict tumor cell dependence upon YAP/TAZ-TEAD, and thus potentially provide a means to identify patients likely to benefit from TEAD inhibitors.2024-01-01T00:00:00Z2024 Feb2026-05-28T03:09:34.865Z2025-02-19T03:10:13.915ZS-EPMC109305323847321410.3390/cancers16050852