Chapter 10: Vascular Effects of Photodynamic Therapy for Tumors

The localized damage of tumor vasculature contributes to the therapeutic effect of photodynamic therapy (PDT) in many of its oncologic uses. As a function of the treatment protocol, vascular effects can manifest as vasoconstriction, vasodilation, hemostasis, and/or hyperpermeability, among other hemodynamic changes. The extent and nature of vascular damage will depend on treatment-specific factors, such as the photosensitizer used (targeted or untargeted, pharmacokinetics and dosing), drug-light interval, and illumination fluence and fluence rate. Moreover, microenvironmental factors specific to the pre-existing structure (e.g., stromal composition) and function (e.g., flow velocity) of tumor blood vessels may determine their sensitivity to PDT. PDT-created vascular damage is integral to the inflammatory response that can accompany it, and may also play a role in the development of anti-tumor immunity. Simultaneous with vascular and immune effects, survival signaling can be activated by PDT, potentially detracting from tumor response. Indeed, combination therapies that include molecular targeting of PDT-upregulated pathways, such as those involved in angiogenesis, have proven beneficial to long-termtumor response. The advantages and limitations of PDT-triggered vascular damage are also evident in its clinical application. Looking ahead, the incorporation of hemodynamic monitoring in clinical trials of PDT may provide a means for individualized optimization of treatment.