Research ArticleCancer

The GAS6-AXL signaling network is a mesenchymal (Mes) molecular subtype–specific therapeutic target for ovarian cancer

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Science Signaling  04 Oct 2016:
Vol. 9, Issue 448, pp. ra97
DOI: 10.1126/scisignal.aaf8175

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Personalizing treatment for ovarian cancer

Most patients with ovarian cancer have advanced-stage disease at diagnosis, and treatment options are mainly palliative. Among the various subtypes of ovarian cancer, the mesenchymal (“Mes”) subtype is particularly aggressive. Antony et al. searched for therapeutic options specific for patients with Mes-type tumors by comparing kinase activity profiles in Mes-type and epithelial (“Epi”)–type tumor cells. Relative to Epi-type cells, an increased abundance and distinct localization and activity signature of the receptor tyrosine kinase AXL were associated with metastatic phenotypes in Mes-type cells. AXL inhibition with the small-molecule drug R428 made the Mes-type tumor cells more “Epi-type” and increased survival in tumor-bearing mice. Thus, AXL inhibitors may halt tumor progression and prolong survival in patients with advanced ovarian cancer.

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