Targeting\nMetastasis in Head and Neck Squamous Cell\nCarcinoma Using Follistatin mRNA Lipid Nanoparticles

Metastatic\nprogression significantly reduces survival rates and\ncomplicates treatment strategies in various cancers. Our study introduces\nan mRNA therapy for metastasis inhibition by targeting activin A overexpression,\na pivotal driver of metastasis and cachexia. Utilizing follistatin\nmRNA lipid nanoparticles, we effectively downregulated activin A both\nlocally in the tumor environment and systemically. This led to a reduction\nin tumor burden and suppression of metastatic spread in a murine head\nand neck squamous cell carcinoma model. Treated mice exhibited minimal\nmetastatic occurrence compared to controls. Additionally, our therapy\npreserved the cross-sectional area of muscle fibers and adipose tissues,\ncombating the muscle and fat wasting typically observed in cancer-associated\ncachexia. The therapy also demonstrated a favorable safety profile,\nunderscoring its potential for clinical translation. By integrating\nmetastasis-suppressing and cachexia-alleviating mechanisms, our approach\nrepresents a promising advancement in comprehensive cancer management.\nConsidering the widespread upregulation of activin A in many cancer\ntypes, our therapy holds considerable potential for application across\na broad spectrum of oncologic treatments.