Targeting Tumor Fibrosis with a Potent Peptide Inhibitor of Fibronectin Assembly

The Kwon Research Group investigates a water-soluble PEGylated Functional Upstream Domain (FUD) peptide based on a fibronectin (FN) binding protein of Streptococcus pyogenes to image and treat breast cancer. PEG-FUD peptide tightly binds the N-terminal 70-KDa domain of FN. We know that FN assembly precedes and controls collagen fibril formation in mammary tumors. We hypothesize that targeting FN assembly by PEG-FUD peptide will inhibit collagen deposition and fiber alignment, resulting in decreased tumor growth and metastatic potential.

Determination of thermodynamic parameters (top) and binding affinity of PEGylated FUD (bottom) to fibronectin using Isothermal Titration Calorimetry (ITC). Adapted from Zbyszynski et al., Pharm Res, 2018.