Grant: CIHR Fellowship

Ocular melanoma is the most common type of eye cancer in adult. Half of the patients with ocular melanoma will develop liver metastasis within 15 years after diagnosis. The median survival time is then only 2-8 months, independently of the successful treatment of the primary tumor. Clearly, new care options are urgently required to help cure these patients. It has been recently established that genes encoding Gq proteins (GNAQ and GNA11) are mutated in 83% of ocular melanomas, unveiling the existence of G protein-driven human malignancies. However, the molecular mechanisms by which these mutations can promote tumor progression remain poorly understood. The objective of our project is to decipher the Gq oncogenic signaling network, with emphasis on a novel downstream target, FAK, in order to find new therapeutic options. To do so we will combine functional and genomic information obtained from standard cell lines, genetically defined mouse models, and cell lines derived from ocular melanoma to understand how Gq activates the tyrosine kinase FAK, and the role of this activation in promoting malignant cell growth. Finally, we will endeavor to translate this deeper understanding of signaling circuitry in ocaular melanoma into new precision cancer care by investigating the pre-clinical outcome of targeting the Gq-FAK pathway. To this end, we will generate a mouse model for ocular melanoma metastasis to evaluate the effect of FAK inhibitors as a monotherapy or in combination with already known and novel chemotherapy agents.