Breast Cancer Chemoresistance Mechanisms Through PI 3-Kinase and Akt Signaling.

摘要

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.