The onset of cancer is due to genetics or carcinogenic factors. A single cell’s DNA mutates and is followed by the rapid expansion of the abnormal cell. The mutations then disturb normal cell function, but are also beneficial for the growth and survival of cancer cells. Tumor cells also differ epigenetically and this is how genes are expressed, rather than the genes themselves.
Even though these epigenetic changes don’t affect the genetic code, the gene function can be strongly disturbed in a similar way, to the benefit of cancer cells. The origins of these epigenetic changes have mostly remained a mystery until now. The scientists investigated one frequent epigenetic alteration called hypermethylation, or the excessive addition of methyl groups to DNA. It silences the expression of tumor-suppressing genes, enabling the aberrant behavior of cells and the excessive growth of tumors.
According to Diether Lambrechts the study shows these epigenetic alterations are caused by the environment of the tumor and specifically by oxygen shortage called hypoxia.
The enzymes that normally remove the methyl groups from the DNA require oxygen. With too little oxygen there is too much methylation retained, causing hypermethylation. Hypoxia explains half of the hypermethylation in tumors. This study was dedicated much to breast tumors, but they also demonstrated this mechanism has similarly broad impact in bladder, colorectal, head, neck, kidney, lung and uterine tumors.
Finding the link between oxygen shortage and tumor growth came from the analysis of over 3,000 patient tumors. Using mice they proved that normalizing the blood supply is sufficient to stop the epigenetic alterations from occurring.
Their new insights can have a potentially huge impact on cancer management because they could use epigenetic aberrations to monitor the oxygen supply to a tumor. This will allow better prediction of tumor behavior and help to make more informed treatment decisions. It also sheds light on existing blood vessels targeting therapies as they don’t just help deliver chemotherapy to the tumor, but inhibits new epigenetic aberrations, helping to make relapses less aggressive and therapeutically beneficial.
Testing is now in progress analyzing whether tumor DNA can be used to predict tumor oxygenation, and new research that focuses on blood vessel normalizing therapies. Perhaps it’s not just possible to inhibit, but maybe even to reverse some of these epigenetic aberrations. I found their results very interesting and promising. Interestingly, we at New Hope Unlimited have used oxygen therapies for years to address cancer and avoid chemotherapy.
– Dr Fredda Branyon