Targeting the Hippo/YAP Pathway in Uveal Melanoma: The Downstream Genetic Effects of Verteporfin Treatment

Uveal melanoma is the most common intraocular cancer in adults. Roughly half of diagnosed patients will develop metastases. 90% of these cases will result in a metastatic spread to the liver with an average survival time of approximately six months. There are currently no treatments for the metastatic form of the cancer. Almost 85% of uveal melanomas contain activating mutations in the oncogenes GNAQ and GNA11, which are known upstream regulators of the oncogenic transcriptional co-activator YAP, making YAP an appealing target for this type of cancer. YAP has been shown to be elevated in a number of human cancers, and is a promising therapeutic target. Specifically the small molecule, Verteporfin, has been shown to selectively bind to YAP, and a number of studies have shown Verteporfin to be a highly effective inhibitor of cell growth and proliferation. However, the genetic effects of Verteporfin treatment have not yet been studied in uveal melanoma. In this study, we monitored the effects of inhibiting the transcriptional activity of YAP on downstream genetic levels of two angiogenic inducers and growth promoters, CYR61 and CTGF. Our preliminary results show that while there was a significant dose-dependent decrease in cell growth, Verteporfin did not appear to significantly affect the expression levels of these two genes