It has been found that the HER2-mediated increases in resistance to multiple chemotherapeutic agents were associated with increased AKT kinase activity and that chemoresistant cells with increased AKT activity were sensitive to selective inhibition of PI3K using specific inhibitors or dominant-negative expression vectors, suggesting that its effects are mediated via PI3K; thus, appropriate combinations of traditional chemotherapeutic agents with new-generation signal transduction inhibitors of the HER/PI3K/AKT pathway may provide clinical advantages in treating breast cancer patients.[114]. This evidence concerns the gene PIK3CA and breast carcinoma.