LAUSR

Simple Summary Cancer is a disease in which cells grow in an uncontrolled manner. This can be due to excessive cell proliferation or reduced cell death or a combination of the two. The Hippo signaling pathway, when misregulated, promotes excessive growth and cancer development by inducing uncontrolled cell proliferation and inhibiting cell death. This is achieved due to unregulated activity of the oncogenic effector of this pathway, YAP/TAZ. Therefore, it is critical to develop inhibitors to disrupt YAP activity in cancers. This article reviews the different types of assays that are used in development of small molecule inhibitors for YAP activity in cancers. Abstract YAP/TAZ are transcriptional coactivators that function as the key downstream effectors of Hippo signaling. They are commonly misregulated in most human cancers, which exhibit a higher level of expression and nuclear localization of YAP/TAZ, and display addiction to YAP-dependent transcription. In the nucleus, these coactivators associate with TEA domain transcription factors (TEAD1-4) to regulate the expression of genes that promote cell proliferation and inhibit cell death. Together, this results in an excessive growth of the cancerous tissue. Further, YAP/TAZ play a critical role in tumor metastasis and chemotherapy resistance by promoting cancer stem cell fate. Furthermore, they affect tumor immunity by promoting the expression of PD-L1. Thus, YAP plays an important role in multiple aspects of cancer biology and thus, provides a critical target for cancer therapy. Here we discuss various assays that are used for conducting high-throughput screens of small molecule libraries for hit identification, and subsequent hit validation for successful discovery of potent inhibitors of YAP-transcriptional activity. Furthermore, we describe the advantages and limitations of these assays.