Targeting Metastasis in Head and Neck Squamous Cell Carcinoma Using Follistatin mRNA Lipid Nanoparticles
Metastatic progression significantly reduces survival rates and complicates treatment strategies in various cancers. Our study introduces an mRNA therapy for metastasis inhibition by targeting activin A overexpression, a pivotal driver of metastasis and cachexia. Utilizing follistatin mRNA lipid nanoparticles, we effectively downregulated activin A both locally in the tumor environment and systemically. This led to a reduction in tumor burden and suppression of metastatic spread in a murine head and neck squamous cell carcinoma model. Treated mice exhibited minimal metastatic occurrence compared to controls. Additionally, our therapy preserved the cross-sectional area of muscle fibers and adipose tissues, combating the muscle and fat wasting typically observed in cancer-associated cachexia. The therapy also demonstrated a favorable safety profile, underscoring its potential for clinical translation. By integrating metastasis-suppressing and cachexia-alleviating mechanisms, our approach represents a promising advancement in comprehensive cancer management. Considering the widespread upregulation of activin A in many cancer types, our therapy holds considerable potential for application across a broad spectrum of oncologic treatments.
Authors
- Daniel L. Marks (ORCID: https://orcid.org/0000-0003-2675-7047)
- Xinxia Zhu (ORCID: https://orcid.org/0009-0009-4041-1561)
- Yulia Eygeris (ORCID: https://orcid.org/0000-0002-8927-5128)
- Babak Mamnoon
- Ariana Sattler (ORCID: https://orcid.org/0000-0003-1699-4743)
- Vladislav Grigoriev
- Parham Diba (ORCID: https://orcid.org/0000-0003-1014-510X)
- Brennan Olson (ORCID: https://orcid.org/0000-0003-2803-5363)
- Abraham S. Moses (ORCID: https://orcid.org/0000-0002-7006-5681)
- Peter R. Levasseur
- Tetiana Korzun (ORCID: https://orcid.org/0000-0002-5871-2778)
- Samuel S. Newton (ORCID: https://orcid.org/0000-0003-0525-1565)
- Oleh Taratula (ORCID: https://orcid.org/0000-0002-6227-9110)
- Ana Paula Mesquita Souza
- Gaurav Sahay (ORCID: https://orcid.org/0000-0003-1071-0500)
- Antony Jozić (ORCID: https://orcid.org/0000-0001-6249-2328)
- Olena Taratula (ORCID: https://orcid.org/0000-0001-8657-036X)
- Constanze Raitmayr
- Jeonghwan Kim (ORCID: https://orcid.org/0000-0002-1697-5107)
- Kongbrailatpam Shitaljit Sharma
- Prem Singh (ORCID: https://orcid.org/0000-0002-0642-9823)
- Yoon Tae Goo
- Ngoc Le
Institutions
- Oregon State University (US)
- Mayo Clinic (US)
- Oregon Health & Science University (US)
- Yeungnam University (KR)
Publication Details
- Journal
- ACS Nano
- Published
- 2024-11-21
- DOI
- https://doi.org/10.1021/acsnano.4c06930
- Citations
- 10
- Primary Topic
- Nuclear Structure and Function
- Type
- article
- Field-Weighted Citation Impact
- 2.34
Funders
- Oregon Health and Science University
- National Institutes of Health
- Knight Cancer Institute, Oregon Health and Science University
- National Cancer Institute
- National Center for Advancing Translational Sciences