Research ArticleCancer

Functional proteomics interrogation of the kinome identifies MRCKA as a therapeutic target in high-grade serous ovarian carcinoma

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Science Signaling  18 Feb 2020:
Vol. 13, Issue 619, eaax8238
DOI: 10.1126/scisignal.aax8238

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Out of the dark, a new kinase target in ovarian cancer

Ovarian cancer is frequently fatal; it is difficult to detect and challenging to treat. Uncovering genetic signatures has done little to improve clinical outcomes. Using cell lines and patient tumors, Kurimchak et al. analyzed the functional kinome of high-grade serous ovarian carcinoma (HGSOC) and identified a relatively uncharacterized kinase called MRCKA, among potentially others, as being important for HGSOC cell survival and tumor growth. Decreasing MRCKA abundance or pharmacologically inhibiting its kinase activity killed HGSOC cells but, as with so many growth inhibitors, led to activation of other survival-promoting kinases in remaining cells. Cotargeting one of these (PAK1) or cotreating cells with platinum-based chemotherapy had greater cytotoxicity. The findings identify multiple potential therapeutic strategies to treat HGSOC and prevent drug resistance in patients.

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