The treatment of PI3KCA-mutant breast cancer brain metastasis with a selective PI3K/mTOR-inhibitor: a preclinical study to evaluate the response to treatment

• Applicant: Dr. Franziska Maria Ippen
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Hematology, Oncology
• Term: from 2016 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 325246018

One of the most common mutations in breast cancer brain metastases is the Phosphatidylinositol-4,5-Bisphosphate 3-Kinase (PIK3CA) mutation, leading to an enhanced activation of the Phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) pathway, which has been shown to be involved in the development, progression, and treatment resistance of this kind of cancer. These results indicate that the PIK3CA mutation could also be a potential therapeutic target for cerebral metastasis. Despite the development of numerous inhibitors targeting this pathway, there are no approved systemic therapies for the treatment of breast cancer brain metastases at present. Furthermore, the efficacy of some targeted therapies used for the treatment of systemic disease is largely unclear in patients with breast cancer brain metastasis. Thus, there is still an urgent unmet need for new targeted therapies, which are able to inhibit the PI3K/AKT/mTOR pathway in breast cancer brain metastasis in order to successfully treat affected patients. The goal of this research project is to evaluate the therapeutic efficacy of the new PI3K/mTOR-inhibitor GDC-0084 in PIK3CA-mutant breast cancer brain metastasis in a xenograft-mouse model in regards to progression-free survival and overall survival by using bioluminescence imaging (BLI).

• DFG Programme: Research Fellowships
• International Connection: USA
• Hosts: Professorin Dr. Priscilla Brastianos; Professor Daniel Cahill, Ph.D.