Do ERBB Receptors Serve as a Nexus for Oncogenic Signals in Uveal Melanoma?

Uveal melanomas (UMs) metastasize at a high frequency, and metastatic UMs are associated with very poor clinical outcomes. Consequently, there is considerable interest in the genetics and biochemistry of UM and how these insights may lead to novel and effective approaches for treating UM. This work reviews evidence that elevated signaling by the CYSLTR2/Gaq/Ga11 pathway drives UM. This work focuses on the large number of signaling pathways that appear to be activated by the CYSLTR2/Gaq/Ga11 pathway in UM, including pathways not thought to be effectors of canonical CYSLTR2/Gaq/Ga11 signaling. This work reviews evidence suggesting that ERBB receptor tyrosine kinases may mediate CYSLTR2/Gaq/Ga11 signaling in UM, thereby accounting for the non-canonical CYSLTR2/Gaq/Ga11 signaling observed in UM. Thus, this work describes novel targets for UM therapy.