Tumor Microenvironment as a Determinant of Photodynamic Therapy Resistance

Abstract

The tumor microenvironment is a complex force to be reckoned with in terms of cancer treatment. Structure and composition of the tumor stroma, oxygenation status within the tumor, and expression and/or activation of proteins that mediate tumor progression can contribute to the efficacy of, or resistance to, various therapeutic modalities. Photodynamic therapy (PDT) is no exception—the oxygenation status and molecular makeup of the tumor and its stroma is critically important to the success of PDT. Moreover, the application of light therapy to a tumor can counteract the therapeutic benefit by altering the microenvironment. For example, PDT is capable of inducing hypoxia which can limit the extent of PDT damage (by consuming oxygen too rapidly), initiating angiogenesis which allows for reestablishment of the tumor vasculature, and activating survival signaling pathways and increasing expression of proteins which promote tumor progression. This chapter highlights key players in the tumor microenvironment that contribute to treatment failure as well as how resistance can be circumvented by overcoming these road blocks. Further, this chapter will discuss various technologies developed to monitor the tumor microenvironment in an effort to improve PDT dosimetry, allowing for personalized treatment that increases therapeutic efficacy.