obscurin-PH

Obscurin-PH is a therapeutic protein domain derived from the giant cytoskeletal protein obscurin, which is normally expressed in breast epithelium but often lost in breast cancer. It acts as a non-chemical inhibitor of the PI3K/AKT signaling pathway by specifically binding and sequestering the p85 regulatory subunit of Phosphoinositide 3-kinase (PI3K). By preventing the assembly and activation of the PI3K complex, obscurin-PH blunts the pro-survival and metastatic signaling of the PI3K/AKT/NF-κB axis. In preclinical models of triple-negative breast cancer (TNBC), obscurin-PH has demonstrated the ability to inhibit cell migration, invasion, and growth. Furthermore, it serves as a chemo-sensitizer that synergizes with doxorubicin, potentially allowing for the use of lower, less cardiotoxic doses of chemotherapy while maintaining therapeutic efficacy.