My name is Eric Nelson and I’m an assistant professor in the department of molecular and integrative physiology at the University of Illinois, the lab’s. Main focus is looking at how cholesterol and various breakdown products of cholesterol impact, breast cancer and the progression of breast cancer about one in eight women will be diagnosed with invasive breast cancer during their lifetime, and we’ve become pretty good at treating the initial disease Or the initial tumor, however, many women will relapse with metastatic disease and that’s, when the cancer spreads from the primary tumor and at that stage of disease we have very few clinical options.
Previous work has shown that women who have high circulating cholesterol levels in their blood are at increased risk of developing metastatic breast cancer.
On the other hand, women taking cholesterol, lowering medications called statins, are less likely to develop metastatic disease based on the results seen in humans.
We decided to test the direct effects of cholesterol and then evaluate how cholesterol might be impacting breast cancer progression using mouse models.
We found that tumors metastasized more in mice, on a high cholesterol diet and when we examined that a little further, we found that it’s, not cholesterol itself.
That was mitigating those effects, but it’s, actually a cholesterol by product or a breakdown product of cholesterol, called 27 hydroxy cholesterol.
We found that 27 hydroxy.
Cholesterol is not working on the cancer cells themselves, but it’s actually working on the immune cells or white blood cells and what it does is it hijacks those cells and redirects them from fighting cancer to promoting cancer.
So this allows the cancer to spread unchecked, because this metabolite is working on the hosts immune system and not the cancer itself.
We think that the same mechanism would apply to almost all solid tumors. In fact, in our new study we’ve shown that this cholesterol metabolite promotes the spread of pancreatic cancer, lung cancer, colorectal cancer and a type of skin cancer called melanoma.
Based on those results, we thought that blocking the synthesis of 27 hydroxy cholesterol might have effects on the spread of many different, solid tumor types.
And so we tested that by using a small drug to block the production of 27 hydroxy cholesterol and found that that led to a reduction in breast cancer metastasis, we thought that blocking the production of 27 hydroxy cholesterol might have beneficial effects against metastatic cancer to test That we took mice and treated them with a drug that inhibits the production of 27 hydroxy cholesterol, and we found that in those mice there was far less breast cancer metastasis.
We’re, currently working with our clinical partners to determine whether the effects we see in mice also hold true in human tissue.
The other thing that we’re currently working on is to develop better inhibitors of 27 hydroxy cholesterol.
We’re hopeful that our studies will lead to new therapeutic options for the treatment of patients with metastatic disease of breast cancer, but also of other solid tumors.