Research ArticleG Protein Signaling

Direct targeting of Gαq and Gα11 oncoproteins in cancer cells

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Science Signaling  19 Mar 2019:
Vol. 12, Issue 573, eaau5948
DOI: 10.1126/scisignal.aau5948

Targeting uveal melanoma

Uveal melanoma (UM) is a common cancer of the eye, and about half of patients with UM develop metastatic disease. Although most cases of UM are driven by constitutively active mutants of the G protein α subunits Gαq and Gα11, therapies that target signaling pathways downstream of these oncogenic drivers have been unsuccessful. Annala et al. provide further evidence of the ability of the cyclic depsipeptide FR900359 (FR) to inhibit oncogenic Gαq/11 signaling in UM cell lines in vitro, particularly by blocking the mitogenic ERK pathway. Furthermore, FR reduced mutant Gαq–driven UM tumor growth in a mouse xenograft model, suggesting that FR or similar compounds should be further investigated for directly targeting oncogenic Gαq/11 proteins in patients with UM.

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