Photodynamic therapy: Combined modality approaches targeting the tumor microenvironment

Background and Objectives: Photodynamic therapy causes direct cytotoxicity to malignant cells within a tumor. Photodynamic therapy (PDT) can also have both direct and indirect effects upon various non-malignant components of the tumor microenvironment. This action can lead to PDT-mediated angiogenesis and inflammation, which are emerging as important determinants of PDT responsiveness. Study Design/Materials and Methods: Preclinical studies have been performed to document how PDT modulates the tumor microenvironment. The expression, function, and treatment relevance of angiogenic growth factors, proteinases, and inflammatory molecules have been monitored following PDT using mouse tumor models. Results: Photofrin-mediated PDT was shown to be a strong activator of VEGF, MMPs, and COX-2 derived prostaglandins within the tumor microenvironment. Inhibitors that target these angiogenic and pro-survival molecules can enhance the effectiveness of PDT. Conclusions: Improvements in PDT tumor responsiveness may be achieved by employing combined modality regimens targeting malignant cells as well as treatment-induced angiogenesis and/or inflammation.