Therapeutic Modification of Hypoxia

Abstract

Regions of reduced oxygenation (hypoxia) are a characteristic feature of virtually all animal and human solid tumours. Numerous preclinical studies, both in vitro and in vivo, have shown that decreasing oxygen concentration induces resistance to radiation. Importantly, hypoxia in human tumours is a negative indicator of radiotherapy outcome. Hypoxia also contributes to resistance to other cancer therapeutics, including immunotherapy, and increases malignant progression as well as cancer cell dissemination. Consequently, substantial effort has been made to detect hypoxia in human tumours and identify realistic approaches to overcome hypoxia and improve cancer therapy outcomes. Hypoxia-targeting strategies include improving oxygen availability, sensitising hypoxic cells to radiation, preferentially killing these cells, locating the hypoxic regions in tumours and increasing the radiation dose to those areas, or applying high energy transfer radiation, which is less affected by hypoxia. Despite numerous clinical studies with each of these hypoxia-modifying approaches, many of which improved both local tumour control and overall survival, hypoxic modification has not been established in routine clinical practice. Here we review the background and significance of hypoxia, how it can be imaged clinically and focus on the various hypoxia-modifying techniques that have undergone, or are currently in, clinical evaluation.

How the histological structure of some lung cancers shaped almost 70 years of radiobiology

“…Over the recent decades, several hypoxia modification strategies have been developed and investigated in an attempt to improve patient outcomes (reviewed by Horsman et al [ 35 ]), however, most reported improvements in outcomes are modest due to the heterogeneity in hypoxia distribution, lack of hypoxia assessment and poor patient selection and stratification in clinical studies [ 14 , 36 ]. One early approach aimed to increase oxygen delivery to tumours by allowing patients to breathe hyperbaric oxygen (100% oxygen) or carbogen (95% oxygen and 5% carbon dioxide).…”

Targeting Hypoxia: Revival of Old Remedies

“…The most relevant approach to overcome tumour hypoxia is to promote oxygen delivery. Hyperbaric oxygen (HBO) treatment consists of breathing 100% oxygen at 2-4 times the normal atmospheric pressure, which results in saturated haemoglobin and increased oxygen in the circulation [5][6][7]. While HBO is applied during or briefly before the radiation treatment, multiple clinical studies, including multi-centre randomised trials by the medical research council (MRC) in late 1970s and mid-1980s, showed that HBO treatment improved local control in patients with head and neck squamous cell carcinoma (HNSCC) or cervical cancer, compared to normal air.…”

Self-Supplying of Hydrogen Peroxide/Oxygen Based on CaO2-Co3O4 Cascade Nanoreactors for Cellular Microenvironment Regulation

“…The tumor cell microenvironment possesses unique characteristics such as acidic pH, hypoxia, overexpressed reactive oxygen species, and reactive sulfur species, 1 which are closely related to the growth, invasion, and metastasis of tumor cells. 2 The dynamic nature of this complex cell microenvironment causes difficulties in efficiently treating cancer. For example, overexpressed H 2 O 2 can induce a high level of reactive oxygen species in cells, which causes cell necrosis or oxidative stress.…”