Major Cause of Cancer Cell Spread – Hypoxia According to new research from the University of Georgia, cellular hypoxia may be a major source of uncontrolled and rapid tumor spread in some cancers. The prevailing view is that genetic mutations cause cancer development. If it turns out that a state of cellular hypoxia is a major driving force in certain types of cancer, then treatment options to control malignant growth could be significantly altered, said Ying Xu, a leading University of Georgia scholar and professor of bioinformatics and computational biology in the Franklin College of Arts and Sciences. The team sampled RNA data, or transcriptional data, from a public database for seven types of cancer. They found that chronic cellular hypoxia may be a major driver of cancer progression. The study was published in the Online Journal of Molecular Cell Biology. Previous studies have pointed to cellular hypoxia as a contributing factor to cancer development, but not a driver of cancer progression. Ying Xu noted that the high incidence of cancer in the world cannot be explained by chance genetic mutations alone. He added that bioinformatics, which integrates biology and computation, has allowed researchers to look at cancer from a whole new perspective. Mutations at the genetic level may give cancer cells a competitive advantage over healthy cells, but his proposed new model of cancer development does not require the usual symptoms of disease, such as the sudden spread of an oncogene – that is a precursor to the emergence of cancer cells. “Cancer drugs try to reach the root of a specific mutation at the molecular level, but cancer tends to bypass it,” says Ying Xu, “so we thought that maybe gene mutations are not the main driver of cancer. Until now, cancer research has mostly focused on designing drug regimens to deal with mutations associated with specific types of cancer. Ying Xu’s group analyzed data downloaded from the Stanford Microarray database to identify abnormal gene expression forms in seven types of cancer — breast, kidney, liver, lung, ovarian, pancreatic and gastric cancers. — abnormal gene expression forms. This online database allows scientists to retrieve information from microarray chips, which are small pieces of glass containing large amounts of genetic information. Ying Xu used the gene HIF1A as a biomarker to indicate the amount of molecular oxygen in the cell. All seven types of cancers showed an increase in the amount of HIF1A, indicating a decrease in the amount of oxygen in cancer cells. Intracellular hypoxia hinders oxidative phosphorylation activity, which is an efficient way for cells to convert nutrients into energy under normal conditions. As oxygen decreases, cells turn to enzymolysis to produce energy units called A TP. Since energy is obtained much less efficiently through enzymolysis, cancer cells must work twice as hard to obtain more nutrients – specifically glucose – in order to survive . When oxygen levels drop to very low levels, the process of growing new blood vessels begins. The new blood vessels provide fresh oxygen, which raises the oxygen level in the cells and tumors, slowing the progression of the cancer – but only temporarily. “Cancer cells grow when they get more nutrients, which makes the tumor biomass larger and more oxygen-deprived. In turn, the efficiency of energy conversion decreases further, causing the cells to become even more starved, prompting them to get more nutrients from the blood flow, and so a vicious cycle develops. This may be a major driver of cancer,” said Ying Xu. This new model of cancer development helps explain why many cancers become drug-resistant quickly, often within three to six months, according to Ying Xu. He stressed the importance of testing this new model through experimental cancer studies. If this model applies, then researchers will need to find ways to prevent cells from developing a hypoxic state, and cancer treatment could change radically. In this sense, oxygen can prevent and treat not only many diseases, but cancer as well. Thus, oxygen is not only the first element of life, it is also the best medicine.