trastuzumab + PTEN mRNA

**Trastuzumab + PTEN mRNA** is an experimental combination therapy designed to address trastuzumab resistance in HER2-positive breast cancer associated with PTEN loss. Trastuzumab is a monoclonal antibody that binds to the HER2 receptor, inhibiting downstream signaling and promoting antibody-dependent cellular cytotoxicity. PTEN mRNA, delivered via tumor microenvironment pH-responsive nanoparticles, restores PTEN expression to block the hyperactivated PI3K/Akt pathway in resistant cells, thereby resensitizing tumors to trastuzumab. This approach targets epithelial-mesenchymal transition (EMT), cancer stem cell expansion, and subtype switching to triple-negative phenotype observed in PTEN-deficient, trastuzumab-resistant cancers. Primary indication is trastuzumab-resistant HER2-positive breast cancer; preclinical studies demonstrate effective systemic mRNA delivery, reversal of resistance, and tumor suppression.[7][9]