Does the ERBB/EGF Signaling Network 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 in how these insights may lead to novel and effective approaches to treating it. This work reviews the biology and pharmacotherapy of UM. It also summarizes signaling by the network comprising ERBB receptor tyrosine kinases and EGF family peptide growth factors, including mechanisms of crosstalk with G protein-coupled receptors. Next, this work discusses signaling changes that appear to drive UM, particularly increased signaling by the CYSLTR2/Gαq/Gα11 pathway. Finally, this work suggests that some of the signaling events that drive UM may be the consequence of crosstalk between the CYSLTR2/Gαq/Gα11 pathway and the ERBB/EGF signaling network. Thus, this work proposes that the ERBB/EGF signaling network may be a novel therapeutic target for UM.