Targeting the Tumor Microenvironment Using Photodynamic Therapy Combined with Inhibitors of Cyclooxygenase-2 or Vascular Endothelial Growth Factor

Photodynamic therapy (PDT) involves the administration of a photosensitizer (PS) followed by localized exposure of a targeted tissue to PS adsorbing light. PDT induces cytotoxicity to exposed malignant cells and also effects non-malignant components of the tumor microenvironment. This indirect action of PDT leads to inflammatory and proangiogenic responses and modulates treatment effectiveness. Preclinical studies designed to determine how PDT modulates the tumor microenvironment use murine tumor models to investigate the expression and/or the activation of growth factors, proteinases, and inflammatory molecules following treatment. These studies demonstrate that improvements in treatment responsiveness following PDT are achieved using inhibitors targeting angiogenic and/or inflammatory pathways.