Research ArticleCancer

Merlin Deficiency Predicts FAK Inhibitor Sensitivity: A Synthetic Lethal Relationship

Science Translational Medicine  21 May 2014:
Vol. 6, Issue 237, pp. 237ra68
DOI: 10.1126/scitranslmed.3008639

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Therapeutic Magic Without Merlin

Mesothelioma is an aggressive cancer of the pleura (lung lining), which is very difficult to treat and often recurs after therapy. Now, Shapiro and coauthors have discovered that mesotheliomas and other tumors that are low in a tumor suppressor called Merlin are particularly sensitive to treatment with a new drug called VS-4718, which blocks the activity of the enzyme focal adhesion kinase. Moreover, in preclinical testing, VS-4718 was particularly effective at killing cancer stem cells, which are the hardest to eradicate with conventional chemotherapy and can give rise to recurrent tumors. These results suggest that VS-4718 or a similar drug may make a valuable addition to the standard treatment regimen for mesothelioma and may reduce the risk of relapse in this cancer.