The Tumor Microenvironment

Among the approaches being studied in this regard are fibroblast activation protein inhibitors targeting the CAFs, CTLA-4 monoclonal antibodies targeting the immune system, kinase inhibitors targeting the signaling pathways, matrix metalloproteinase inhibitors targeting the ECM, and vascular endothelial growth factor inhibitors targeting tumor angiogenesis. Co-administration of the angiotensin inhibitor losartan has been found to sensitize pancreatic cancer to neoadjuvant FOLFIRINOX chemotherapy and improve outcomes by modifying the microenvironment, increasing drug and oxygen delivery to cancer cells, and activating immune pathways. The many successes of oral metronomic chemotherapies can be attributed to the normalization of tumor vasculature, inhibition of endothelial cell proliferation and migration, increased expression of the antiangiogenic protein thrombospondin-1, suppression of Tregs, functional restoration of NK cells and cytotoxic T-cells, and induction of dendritic cell maturation.