Tumor Hypoxia

The equally intriguing phenomenon of tumor hypoxia has been documented to occur in a number of tumor types including cancers of the uterine cervix , head and neck , bladder as well as in soft tissue sarcomas . This is the result of inadequate blood supply to tissues that leads to the compromise of biological function and in the case of cancers this is usually related to abnormal or inadequate blood vessels, anemia, or the formation of methemoglobin or carboxyhemoglobin that will reduce the oxygen carrying capacity of the blood in smokers. 

There have been several observations collected over the last few decades that suggest that tumor hypoxia plays a key role in outcome. These observations are as follows: tumors often have lower median partial pressures of oxygen than their tissues of origin ; the presence of tumor hypoxia cannot necessarily be reliably predicted by factors like stage, size, histology, or grade; tumor-to-tumor oxygen variability is often greater than intratumor oxygenation 

differences , and recurrent tumors often are more poorly oxygenated than their corresponding primary tumor.

While the controversy about the exact role that anemia plays in determining outcome from radiation therapy is age old, i.e., big tumors bleed more and are more likely to spread vs tumors in anemic patients tend to be more hypoxic and hence more resistant to therapy, evidence is accumulating to suggest that reality is firmly rooted between both views. Radiosensitivity is known to be significantly limited when the partial pressure of oxygen is less than 25–30 mmHg. 

It has been known for years that molecular oxygen will increase radiation-induced DNA damage through the formation of oxygen free radicals that act to inflict “indirect” damage beyond the “direct” effects of radiation on DNA . There is also substantial evidence obtained over the last few years that tumor hypoxia induces genomic changes with subsequent upregulation of genes that are linked to radiation resistance . Equally compelling are the experiments that have revealed that presence of tumor hypoxia is linked to an increased incidence of metastatic disease .
The microenvironmental signals in a hypoxic tumor environment are such that there is greater genomic instability and selection pressure to maintain those cells with increased angiogenic potential and decreased apoptotic potential. Improved understanding of this interesting phenomenon will ultimately lead to improved potential for therapeutic targeting of tumors.