Elucidating resistance to AKT inhibition in metastatic breast cancer

AKT Inhibition has emerged as one of the most promising targeted therapies for breast cancer. In triple negative breast cancer with pathway mutations, AKT inhibition has substantial efficacy with paclitaxel. In ER positive breast cancer, capivasertib has substantial activity in AKT1 mutant breast cancer and in combination with fulvestrant. Yet there is very limited understanding of clinically relevant resistance mechanisms. We will use breast cancer
patient derived models, both organoid and xenograft, to study mechanisms of acquired resistance to AKT inhibitor
resistance, combined with patients' material from AKT inhibitor clinical trials, to identify and validate mechanisms
of resistance.