FAM83 proteins: Fostering new interactions to drive oncogenic signaling and therapeutic resistance

The FAM83 proteins were recently identified as novel transforming oncogenes that function as intermediaries in EGFR/RAS signaling. Using two distinct forward genetics screens, the Bissell and Jackson laboratories uncovered the importance of the FAM83 proteins in promoting resistance to EGFR tyrosine kinase inhibitors and therapies targeting downstream EGFR signaling effectors. The discovery of this novel oncogene family using distinct genetic screens provides compelling evidence that the FAM83 proteins are key oncogenic players in cancer-associated signaling when they are overexpressed or dysregulated. Consistent with a role in oncogenic transformation, the FAM83 genes are frequently overexpressed in diverse human cancer specimens. Importantly, ablation of numerous FAM83 members results in a marked suppression of cancer-associated signaling and loss of tumorigenic potential. Here, we review the current knowledge of the FAM83 proteins' involvement in cancer signaling and discuss the potential mechanisms by which they contribute to tumorigenesis. Both redundant activities shared by all 8 FAM83 members and non-redundant activities unique to each member are highlighted. We discuss the promise and challenges of the FAM83 proteins as novel points of attack for future cancer therapies.