Development FAP-Targeted Nanotherapy against Cancer-Associated Fibroblasts

Extended Abstract In the recent years, cancer research has largely focused on biology of cancer-related stroma. The tumor microenvironment (TME) is a highly heterogeneous milieu consisting of different cell types and plays an important biological role in cancer development and progression. In particular, cancer-associated fibroblasts (CAFs) are the major cell population in the TME which support tumor growth, metastasis formation and induce drug resistance, through the production and secretion of variety of growth factors and cytokines, as well as extracellular matrix components [1]. A biological hallmark of CAFs is the selective expression of fibroblast activation protein (FAP), a membrane-bound serine protease of the dipeptidyl peptidase subfamily, not present in healthy tissues [2]. FAP is important for remodeling in FAP-overexpressing cells. Finally, we evaluated biodistribution and tumor targeting of HFn-FAP in a mouse syngeneic model of triple negative breast cancer after intravenous administration. In vivo preliminary results demonstrated that functionalized HFn is able to recognize CAFs and enhance intratumoral retention of the nanoparticles. In conclusion, our findings suggest that FAP-targeted nanotherapy could be a promising strategy against CAFs to modulate the tumor microenviroment and provide new hope to fight the cancer.