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