Targeting Lung-Derived Proteins as a Therapeutic Strategy Against Breast Cancer Metastasis
Abstract
Therapy for lung metastasis is often given systemically, causing significant toxicity. However, the lung holds potential for direct targeting via inhaled drugs; an approach that has shown promise in treating respiratory diseases but remains underexplored in oncology. This project tested the hypothesis that CD44-interacting proteins produced in the lung promote breast cancer metastasis and can be targeted directly using inhalable drug delivery. The major findings of the project are that the CD44-interacting proteins OPN, FGF2, and E/P/L selectins have complementary and important roles in mediating breast cancer metastatic behavior in response to the lung microenvironment. OPN and selectins (but not FGF2) were found to be necessary for metastatic colonization of the lung, particularly for more aggressive breast cancer cell lines. The pan-selectin antagonist bimosiamose was chosen for further study and subjected to drug formulation, optimization and quality assurance into an inhalable inhibitor that was tested in vivo for its ability to reduce breast cancer lung metastasis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2021
- Accession Number
- AD1153331
Entities
People
- Alison Allan
- Raimar Loebenberg
Organizations
- Western University