Human malignant mesothelioma NCI-H226 cells treated with TEAD inhibitor K-975 in SCID mice.

We investigate the dependence of human malignant mesothelioma on functional TEAD transcription factors to maintain fully established tumors in vivo. We show that TEAD inhibitor K-975 stops tumor growth in vivo, eventually causing tumor regression, by downregulating TEAD activity and altering, thus, TEAD-dependent transcription in a dysfunctional Hippo genetic background. Our data  validate the concept of inhibiting an activated YAP1/TEAD complex for the treatment of malignant pleural mesothelioma patients. Five replicate mice per treatment group were inoculated subcutaneously with NCI-H226 cells and treated with three different doses of K-975, or with the vehicle. Tumors were removed at four different time-intervals after treatment.  Two untreated groups served as controls. Whole transcriptomes were evaluated by RNA-seq. One vehicle sample dropped out.