Targeting Tumor Hypoxia in Radiotherapy: A Brief Review of Historical Background and Recent Progress

Abstract

Tumor hypoxia is a physiologic barrier to radiotherapy and anti-tumor drug delivery. Numerous efforts have been made to overcome this barrier and to improve therapeutic outcomes. Strategies for targeting tumor hypoxia have included chemical radiosensitizers and hyperthermia, followed by combined synergic therapeutic modalities. Clinical hypoxia measurements and the development of molecular imaging agents prompted trials on dose escalation in external beam radiotherapy, which takes advantage of contemporary sophisticated radiation dose delivery techniques. Increases in our understanding of hypoxia-induced biological pathways have led to the investigation of various hypoxia targeting drugs. Radiolabeled hypoxia targeting drugs deliver radionuclides into hypoxic tumor cells and achieve highly localized cell death. In this manuscript, we briefly review the methods of targeting tumor hypoxia in radiotherapy. These include image guided dose escalation in external beam radiotherapy, radiosensitizers, and radiolabeled agents targeting hypoxia pathways and the receptors on hypoxic tumor cells. Our current understanding of tumor hypoxia is the culmination of the collective efforts of generations of researchers. New frontiers are continuing to expand, as new discoveries are being made on both the macroscopic and molecular levels.

Assessment of Serum Hypoxia Biomarkers Pre- and Post-radiotherapy in Patients with Brain Tumors

“…The majority of clinical efforts to combat tumor hypoxia have provided conflicting results. Because of better knowledge of the biological mechanisms driven by hypoxia and the disclosure of new hypoxia biomarkers, targeting hypoxia has become more plausible (Zhang et al 2016).…”

“…The majority of clinical efforts to combat tumor hypoxia have provided conflicting results. Because of better knowledge of the biological mechanisms driven by hypoxia and the disclosure of new hypoxia biomarkers, targeting hypoxia has become more plausible (Zhang et al 2016 ). The main target of this study was to assess the circulating serum hypoxia biomarkers HIF-1α, VEGF, osteopontin, erythropoietin, caveolin-1, GLUT-1, and LDH pre- and post-radiotherapy in patients with brain tumors.…”

Targeted Anti-Cancer Provascular Therapy Using Ultrasound, Microbubbles, and Nitrite to Increase Radiotherapy Efficacy

“…Note that several subtypes can further refine this classification . Recent literature suggests that it would be more important to target acute hypoxia rather than chronic hypoxia in the treatment of cancer, as acutely hypoxic cells have a greater metastatic potential than chronically hypoxic cells. , Interestingly, increasing blood perfusion in tumors could address both types of hypoxias by increasing the overall oxygen supply and by reperfusing transiently underperfused acutely hypoxic areas. Provascular therapies, such as sodium nitrite, sodium nitroprusside, or nitroglycerin administration, aim at momentarily increasing the supply of blood, therefore oxygen, to hypoxic tumors in order to subsequently improve the efficacy of RT.…”