Cancer cells in breast tumors can produce their own estrogen, which not only fuels their growth but also helps prevent them from dying. Blocking estrogen production is one way of treating these cancers, but also often produces side effects like cognitive deficits or osteoporosis in patients.

Now, a researcher in Texas is trying to figure out how to block the production of estrogen only in cancer cells and prevent these unwanted side effects in the brain or bone. Kevin Pruitt was recruited with the help of a CPRIT Rising Stars Award to Texas Tech University Health Sciences School of Medicine from Louisiana State University Health Sciences Center, where he holds the position of Associate Professor in the Immunology and Molecular Microbiology Department.  In 2017 he was chosen as the inaugural recipient of the Childers-Fralick Chair in Basic Cancer Research and in 2018 he was conferred the title of University Distinguished Faculty.

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Cancer cells in breast tumors can produce their own estrogen, which not only fuels their growth but also helps prevent them from dying. Blocking estrogen production is one way of treating these cancers, but also often produces side effects like cognitive deficits or osteoporosis in patients.

Now, a researcher in Texas is trying to figure out how to block the production of estrogen only in cancer cells and prevent these unwanted side effects in the brain or bone. Kevin Pruitt was recruited with the help of a CPRIT Rising Stars Award to Texas Tech University Health Sciences School of Medicine from Louisiana State University Health Sciences Center, where he holds the position of Associate Professor in the Immunology and Molecular Microbiology Department.  In 2017 he was chosen as the inaugural recipient of the Childers-Fralick Chair in Basic Cancer Research and in 2018 he was conferred the title of University Distinguished Faculty.

In postmenopausal women, even after their ovaries have stopped producing estrogen, an enzyme called “aromatase” converts an estrogen precursor into estrogen in tissues that need it for basic biological functions, like the brain, bone, and skin. Some breast tumor cells not only gain the capacity to make their own estrogen using aromatase, but the enzyme also becomes hyperactive, helping assure the cancer cell’s immortality.

Drugs that block aromatase can be an effective type of breast cancer chemotherapy. But this also blocks aromatase activity everywhere in the body, making this therapy very hard on tissues that ordinarily rely on the small amounts of estrogen they can produce themselves.

Pruitt’s approach is to look further upstream for ways to block a tumor’s estrogen production. The molecules in cells that affect the activity of aromatase in cancer cells are different from the ones that regulate aromatase in other tissues. Pruitt is trying to utilize that difference to selectively block aromatase only in tumors. If he’s successful, a therapy to shut down the unhealthy, life-prolonging production of estrogen in tumor cells wouldn’t affect the life-sustaining estrogen in normal tissues.

Another project Pruitt is working on is understanding the epigenetics of cancer; learning about changes in a tumor cell’s genome that enable the cell to withstand stresses that would kill a normal cell. While all cells in the human body have the same genome, not all of those genes will be expressed in every tissue. So-called epigenetic changes may involve small molecules being added to or removed from a cancer’s DNA to either turn on or silence certain genes. These changes help a cancer cell withstand radiation and chemotherapy and also make it more resistant to attack from the immune system.

Pruitt hopes that better understanding how these changes happen inside cells can lead to targeted therapies to reverse them. “We can potentially come up with ways to target a cancer cell and disable that capacity that it’s gained,” Pruitt says, “because often times what it has gained is based on an epigenetic change that’s reversible.”

If he can figure out how to make a cancer cell more susceptible to the immune system, for example, this epigenetic therapy could be used in combination with immune therapy to give cancer a one-two knockout punch—even in a tumor that might be resistant to either therapy on its own.

Pruitt was born in Houston and received his undergraduate training in chemical engineering from the University of Texas at Austin. He received his Ph.D. in pharmacology from the University of North Carolina, Chapel Hill. He was a postdoctoral fellow in oncology at Johns Hopkins University School of Medicine and a fellow at the Sidney Kimmel Comprehensive Cancer Center, prior to joining the faculty at LSU in 2006.  

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