Oncogenic shock: Turning an activated kinase against the tumor cell

  • Sharma S
  • Settleman J
  • 16


    Mendeley users who have this article in their library.
  • 23


    Citations of this article.


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.

Author-supplied keywords

  • Cancer therapeutics
  • Kinase inhibitors
  • Oncogene addiction
  • Oncogenic shock
  • Signal transduction
  • Tyrosine kinases

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Get full text


  • Sreenath V. Sharma

  • Jeffrey Settleman

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free