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PIK3CA is the most mutated gene in breast cancer and is important in other cancers. An integral part of the PI3K pathway, PIK3CA is an oncogene with two hotspots for activating mutations: the 542/545 region of the helical domain and the 1047 region of the kinase domain. The interaction of PIK3CA with the AKT and mTOR pathways is the subject of an immense amount of research and development, and PI3K inhibitors have exhibited some success in recent clinical trials. While PI3K monotherapies are likely insufficient, there is interest in pursuing PI3K inhibition in combination with other therapies including TKI's, MEK inhibitors, PARP inhibitors, and - in breast cancer - aromatase inhibitors. |
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