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.
Ferrario
Angela
A
The Saban Research Institute, Childrens Hospital Los Angeles, University of Southern California, Los Angeles, CA, USA.
Gomer
Charles J
CJ
D000818:Animals; D000068579:Celecoxib; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D003131:Combined Modality Therapy; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D017323:Dihematoporphyrin Ether / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D006801:Humans; D007267:Injections; D008027:Light; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009578:Nitrobenzenes / Q000494:pharmacology / Q000627:therapeutic use; D010778:Photochemotherapy; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D012867:Skin / Q000187:drug effects / Q000528:radiation effects; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays
D052246:Cyclooxygenase 2 Inhibitors; D009578:Nitrobenzenes; D011720:Pyrazoles; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D017323:Dihematoporphyrin Ether; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D015232:Dinoprostone