Breast Cancer Chemoresistance Mechanisms Through PI 3-Kinase and Akt Signaling
Technical Report,01 May 2012,30 Apr 2015
Beth Israel Deaconess Medical Center Boston United States
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We have discovered that the Akt pathway modulates breast cancer cell survival in response to genotoxic agents, and discovered a new substrate of Akt,MERIT40, that is phosphorylated upon exposure of cells to chemotherapeutic drugs. We propose that this represents a major mechanism by which cells exposed to these drugs evade cell death by apoptosis and thus become resistant to the damaging effects of clinically-relevant chemotherapy agents. These findings have important ramifications for the use of chemotherapy drugs in breast cancer patients, and many also suggest that MERIT40 may be used as a clinically relevant biomarker for resistance to doxorubicin.