Non-muscle myosin II 2026

Background: Non-muscle myosin IIA (NMIIA; encoded by MYH9) has been implicated in breast cancer progression; however, its clinical significance and therapeutic potential in HER2-positive (HER2+) breast cancer remain poorly defined. We investigated the clinical significance of NMIIA and evaluated the anti-tumour activity of the selective NMII inhibitor MT-228.
Methods: NMIIA expression was evaluated by immunohistochemistry in a cohort of 1,142 patients with early-stage invasive breast cancer. Molecular docking and molecular dynamics simulations were performed to characterize binding of MT-228 to NMIIA. The effects of MT-228 were assessed in breast cancer cell lines using assays of cell viability, migration, three-dimensional invasion, DNA damage, apoptosis, and combination studies with FDA approved HER kinase inhibitors Neratinib and Tucatinib.
Results: High NMIIA expression was associated with adverse clinical outcomes in patients with HER2 immunoreactive breast cancer. Computational analyses demonstrated that MT-228 forms favorable binding interactions and stabilized the NMIIA motor domain. MT-228 inhibited cell growth across multiple breast cancer subtypes. In HER2+ cell lines, MT-228 suppressed migration and 3D invasion, increased γH2AX foci formation, caspase-3/7 enzyme activity, and PARP cleavage, and enhanced the anti-proliferative activity of Neratinib and Tucatinib.
Conclusions: Our findings identify NMII as a potential therapeutic target in HER2 immunoreactive breast cancer and support further investigation of selective NMII inhibition either alone or in combination with anti-HER therapies.