Abstract
The transcriptional co-activators YAP and TAZ are key drivers of adult stem cell proliferation and are potent oncoproteins in many human cancers. I will describe our ongoing target validation efforts with YAP/TAZ in both squamous cell carcinoma and colorectal cancer, two of the most common human cancer types. Through the combination of mouse genetics and human cancer cell and organoid culture, we can demonstrate that targeting YAP/TAZ will be of therapeutic benefit in these cancer types. Of key interest is the notion that YAP/TAZ not only drives cell survival and proliferation, but also drives inflammation and immune evasion. Thus, targeting YAP/TAZ may not only impair tumour growth, but also make it possible to overcome resistance to immunotherapy. I will also describe our drug development efforts, including novel compounds that can potently inhibit YAP/TAZ activity with excellent tolerability and pharmacokinetics.
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