In a study that will be published in the upcoming edition of Cancer Research, scientists in the Medical Center have made a discovery that runs contrary to existing paradigms about tumor cell growth.
"It's a common belief that to cause mutations in the cell you have to have... direct damage to the DNA," said Chuan-Yuan Li, assistant research professor of radiation oncology and the study's lead author. "[We found] that if you have other stresses not known to be directly damaging to the DNA-such as heat or a lack of oxygen-these also tend to increase the mutation rate in cancer cells."
Li explained that this finding is important because it could help explain increased incidence of mutations in cancer cells and potentially help improve chemotherapy treatments.
"People have known that tumors start out benign, turn malignant and then get worse," said Mark Dewhirst, professor of radiation oncology and the study's co-author. "But they haven't understood this progression or why [the tumors] become genetically unstable."
Although the research team is still far from understanding the intricacies of the mutation process, the latest finding sheds some light on why cancer cells have such high mutation rates.
Currently, scientists have pinpointed causes of high mutation levels for only a handful of cancer types-those in which the cell's ability to repair its own DNA has been lost. When a cell can no longer repair its own DNA, the chances of a mutation during cell division jump from one-in-a-million to one-in-a-thousand.
But in many cancers, the cells have retained this self-repair ability, leading researchers to believe that there is more to cancer than chance alone. This latest discovery may very well prove to be one of the missing pieces of this puzzle.
Tumors grow so fast that the blood vessels cannot keep supplying them with the necessary oxygen, first creating flow instabilities and eventually leading to a lack of oxygen-a condition known as hypoxia. When the cell finally receives the necessary oxygen the chemical interaction releases free radical molecules that, in turn, cause genetic mutations within the tumor.
The research could also have a significant impact on the overall understanding of how some cancer cells develop resistance to common chemotherapy procedures. Scientists currently believe that cancers become impervious to certain drugs because the only cells that continue to reproduce are the resistant ones. But Li's and Dewhirst's research may prove that these mutations develop during the treatment as a result of certain stresses such as heat or oxygen deprivation.
Li said that the research team can take several directions in future research, either identifying the genes that may be responsible for the mutations or attempting to induce cancer in normal cells with use of these DNA stresses.
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