Starting with the ABCs: Akt in breast cancer.

摘要

In 2002, our group hypothesized that activation of the PI3K/Akt pathway might be an important mechanism of therapeutic resistance in breast cancer, because molecular alterations commonly observed in breast cancer specimens, such as overexpression of HER2 or ER/PR, had been shown to activate this pathway. We demonstrated that in a panel of breast cancer cell lines differing in HER2 and ER/PR status, drugs normally employed in the treatment and management of breast cancer (trastuzumab, tamoxifen, paclitaxel, doxorubcin, etoposide) rapidly activated the serine threonine kinase AKT. This increase in AKT activity allowed cells to evade the cell death normally induced by these drugs, because pharmacologic or genetic inhibition of the pathway increased sensitivity to these drugs.