Genetic Predisposition to Cancer

Oct 19, 2018

Cancer is a dreaded diagnosis. But imagine having a genetic predisposition to getting many types of cancer, passing it from generation to generation. That’s what Li Fraumeni Syndrome, or LFS, is. Texas Tech Health Sciences Center’s researcher says he has evidence in studies with mice that has the potential to help those affected by the rare condition.

Eric and Ashley Finley were ready to start a family. But she had concerns. Eric had just overcome thyroid cancer diagnosis at age 30. And he had lost two family members to the disease when he was young. Eric says they decided to go see geneticist.
 

“She quickly identified what they say is a pretty classic Li Fraumeni pattern,” Eric says, “which is a family member number one, would have been my sister with a certain type of cancer. A family member number two, my father, with a certain type of cancer. And then any other family member, me number three, who had any type of cancer.”

Li Fraumeni, named after the two doctors who discovered it in the late 1960s, can lead to certain, often rare, cancers, and is relatively rare. Researchers used to believe it occurred in as few as one in 10,000; now data show it could be in one in 2000.

The culprit in Li Fraumeni is a mutation in the gene that gives chemical instructions for what’s called tumor protein p53. It acts to suppress tumor growth by regulating cell division by keeping cells from growing and dividing (proliferating) too fast or in an uncontrolled way.

“Asking my mom at the time, what’s wrong with our family, you know and of course no one knew,” he says. “I knew cancer was part of my family, but it never occurred to me that there was something genetically wrong. I just chalked it up to bad luck. So finding out that there was something that you could point to was I think very beneficial.”

Dr. Sanjay Awasthi, a hematology and oncology professor at Texas Tech’s Health Sciences Center and medical director of the Southwest Cancer Center Lubbock, has studied Li Fraumeni in mice for years before arriving in Lubbock in 2016.

He says he’s found first-time evidence that depleting or blocking RLIP, another protein inside a mouse’s p53 protein cell, can stop or prevent cancer’s growth in Li Fraumeni patients like Eric.

“If you look at it from my perspective, knowing what oncologists know about p53 and how patients with Li Fraumeni and these mice get cancer, to me it was kind of a no-brainer that that was a mechanism of how cancer was being prevented,” Awasthi says.

Awasthi says he’s also shown inhibiting RLIP on the outside of the cell with antibodies results in a similar outcome as does depleting the protein from inside the cell.

“We give those antibodies to the mice, the tumor also disappeared. So the antibodies don’t get inside the cell, they only stay at the surface,” he says. “So, here we had sort of proof that either you deplete RLIP inside or just block its function from the outside and you get cell death.”

Awasthi’s research on RLIP depletion was published earlier this year in the Proceedings of the National Academy of Sciences, the official peer-reviewed journal of the National Academy of Sciences. He’ll continue his work with RLIP depletion using a three-year, $1.14 million grant from the Department of Defense to study how to prevent breast cancer.

The Finley’s now have two children, Sam and younger sister Kate. She inherited her dad’s Li Fraumeni. Twice a year she and her dad visit MD Anderson in Houston, where they each get for full-body MRIs and various other scans. Eric says he’s patient and hopeful.

“I think we’ll wait and see what it is,” he says. “You know how the FDA works and so it’s a slow process, it’s not going to be available tomorrow. It’s not going to be available in a couple of years. It’s down the road, so we’re obviously going to have to wait and see but I’m very glad that there one day might be something out there that we can consider doing.”