Researchers at the Duke Cancer Institute have discovered that breast cancer cells make use of cholesterol to build resistance to stress, thus making them immune to treatment as they move away from their original position. The research went into depth to understand the mechanism by which the breast cancer cells develop tolerance to stress.
Commenting on the findings, Donald P McDonnell, professor in the departments of Pharmacology and Cancer Biology and Medicine at Duke University School of Medicine, said, "Most cancer cells die as they try to metastasize -- it's a very stressful process. The few that don't die have this ability to overcome the cell's stress-induced death mechanism. We found that cholesterol was integral in fueling this ability."
As part of their study, researchers studied the link between high cholesterol and estrogen-positive breast and gynaecological cancers. This research led to the discovery that cancer cells originating from the estrogen hormone got energy from cholesterol derivatives, which behaved like estrogen, thus helping the cancer cells to grow and multiply.
The findings, however, were different in the case of estrogen-negative breast cancers. As the name suggests, they do not need estrogen for their survival, so researchers concluded that some other mechanism was functioning in this case. During the research, tests done on cancer cell lines and mouse models revealed that the migrating cancer cells consume cholesterol as a defensive mechanism to stress or outside forces. And in most cases, the cells die and thus stop spreading to different parts of the body.
However, in certain cases the cancer cells are seen overcoming ferroptosis, a natural process in which cells die due to stress. These stress-impervious cancer cells then multiply and easily metastasize all over the body.
The research also understood that the process was used not just by ER-negative breast cancer cells, but also other tumors like melanoma as well. Researchers believe that this process can be improved by therapies. And the mechanisms identified could be targeted by therapies.
McDonnell, who also co-authored the research, said, "Unravelling this pathway has highlighted new approaches that may be useful for the treatment of advanced disease. There are contemporary therapies under development that inhibit the pathway we've described. Importantly, these findings yet again highlight why lowering cholesterol, either using drugs or by dietary modification, is a good idea for better health."
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