Basic Reflections on Tumor Hypoxia

Abstract

As tumors grow, there is rapid constriction and distortion of the small blood vessels that supply oxygen and clear the deoxygenated blood from the tumor, resulting in hypoxia and a necrotic tumor interior. Poor oxygenation is common in some microbial afflictions where bacteria grow and produce biofilms. As described in Chapters 1 and 2, photodynamic therapy utilizes the oxygen in the tumor to produce reactive oxygen species to destroy the tumor, further depleting oxygen from an already poorly oxygenated tumor microenvironment, potentially rendering photodynamic therapy ineffective. This is the hypoxia challenge in anticancer and antimicrobial photodynamic therapy. Recognized by researchers as having the potential to curtail the development and translation of photodynamic therapy and its combinations to the clinic, it triggered the development of several approaches to circumvent it. A dominant approach utilizes nonreactive oxygen carriers such as hemoglobin, perfluorocarbons, microbubbles, and nanobubbles. The second approach utilizes materials that react in situ to produce molecular oxygen. The third approach regulates the tumor microenvironment to improve oxygenation. Hypoxia is also overcome by specific blocking of the hypoxia-inducible factor 1-alpha protein complex which increases oxygen transport. Furthermore, researchers have recognized strategies that are independent of systemic oxygenation, those that moderate the utilization of oxygen, and those that provide oxygen supplementation in the tumor microenvironment. These discussions in this chapter will elucidate the current status of the research and innovation.