Alteration of Akt activity increases chemotherapeutic drug and hormonal resistance in breast cancer yet confers an achilles heel by sensitization to targeted therapy

Breast cancer is a common disease which affects women and men in the prime of their lives. Unfortunately there is no common magic bullet which can effectively cure all breast cancers. Breast cancer arises from many diverse genetic mechanisms. Frequently breast cancer becomes resistant to various therapies and residual, dormant, senescent, drug resistant breast cancer cells resume their growth and often metastasize to other sites. At this point, therapeutic options are limited and we desperately need more effective treatments. This chapter has focused on the key roles that the PI3K/PTEN/Akt/mTOR pathway plays in breast cancer drug resistance and induction of cellular sensecence. Furthermore, breast cancer cells which proliferate in response to this pathway may have an Achilles heel and are highly sensitive to mTOR inhibitors. © 2008 Elsevier Ltd. All rights reserved.