Photodynamic therapy: combined modality approaches targeting the tumor microenvironment.
OBJECTIVE
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.


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.
Gomer
Charles J
CJ
The Saban Research Institute, Children's Hospital Los Angeles, University of Southern California, Los Angeles, California 90027, USA. cgomer@chla.usc.edu
Ferrario
Angela
A
Luna
Marian
M
Rucker
Natalie
N
Wong
Sam
S
D000818:Animals; D003131:Combined Modality Therapy; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D017323:Dihematoporphyrin Ether / Q000494:pharmacology; D004195:Disease Models, Animal; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D017319:Photosensitizing Agents; D042461:Vascular Endothelial Growth Factor A; D017323:Dihematoporphyrin Ether; D051546:Cyclooxygenase 2; D020782:Matrix Metalloproteinases