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Perspectives
“Oncogenic Shock”: Turning an Activated Kinase against the Tumor Cell
Sreenath V. Sharma and Jeffrey Settleman
volume 5 | issue 24
15 december 2006Pages: 2878 - 2880
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Accumulating evidence indicates that mutationally activated kinases are especially good targets for anti-cancer drugs. It has been suggested that this reflects a state of “oncogene addiction” of tumor cells. We recently reported experimental studies that may provide a molecular mechanism to explain such apparent dependency. We find that oncogenic kinases produce both pro-survival and pro-apoptotic signals that decay at different rates upon oncogene inactivation. Pro-survival signals are rapidly attenuated, whereas pro-apoptotic signals are relatively longer-lived. This differential signal decay creates a temporal window during which pro-apoptotic outputs from the oncogenic kinase predominate to actively promote tumor cell death upon kinase inhibition. We refer to this mechanism as “oncogenic shock”, and suggest that it has significant implications for the optimal therapeutic use of targeted kinase inhibitors.
Authors
Sreenath V. Sharma
Center for Molecular Therapeutics, Massachusetts General Hospital Cancer Center, Harvard Medical School; Charlestown, MA USA
Jeffrey Settleman
Massachusetts General Hospital Cancer Center
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.