Cancer, egg similarities allow for targeted strikes, UVa researchers say

Posted: Saturday, September 12, 2015 2:54 pm - Culpeper Star-Exponent - See Original Here

Cancer, egg similarities allow for targeted strikes, UVa researchers say

The quest to better prevent a pregnancy may have resulted in a better way to treat a cancer.

Two University of Virginia School of Medicine researchers studying possible contraceptive uses of human reproductive cells discovered an unexpected link between human eggs and cancer tumors — both often contain a protein called SAS1B.

That may not seem exciting, but the researchers say it is.

“It’s really a great find because it means we can target a cancer cell specifically using that protein,” said John Herr, a researcher with UVa’s Department of Cell Biology who normally delves into the intercellular intricacies of human reproduction.

“This can allow us to create a specific treatment for a cancer, attack it from inside the cell and leave the healthy cells alone,” he said. “That means we can use less of a drug, which means fewer side effects for patients.”

Herr, research partner Eusebio Pires and their contingent of technicians and researchers at the UVa Center for Research in Contraceptive and Reproductive Health were investigating the protein, created only by those egg cells preparing for eventual release and fertilization.

Their idea was to use the protein as a target for a contraceptive by developing sort of an intracellular bomb that could deliver medication to the egg with the protein as a target. Being as the protein is present in the human body only on those eggs getting ready for release into the fallopian tubes, the method could prevent eggs from being fertilized without impacting dormant eggs or the rest of a woman’s body, a problem with current contraceptives based on steroidal hormones such as estrogen and progestin that impact the entire endocrine system.

Then came a “what the heck” moment.

“Except for the small group of growing eggs in the ovary, the SAS1B protein is virtually absent in other tissues in the body,” said Pires, a biologist with the school’s Department of Obstetrics. “Our original focus was on utilizing the protein as a contraceptive but when we looked into previous research on SAS1B we saw where it was found in uterine tumors. We wondered why the hell it was being expressed in tumors when the only other location for it is in egg cells.”

The discovery sent Pires and associates on a four-year mission to try to locate the protein in other cancers even as the researchers continued looking into ways to create a contraceptive.

The search proved fruitful. The protein was discovered in upwards of 70 percent or more of uterine and ovarian cancers and more than half of tumors sampled in breast cancer. Other instances were found in renal, head and neck and pancreatic cancers and some melanomas.

“We had enough information to say that a lot of cancer tumor cells were de-differentiating back to the egg stage. That means they were changing from what they were originally intended to do by developing a protein only found in the egg cells,” Herr said.

That was a eureka moment. If the protein could be used to deliver contraception to egg cells, it could deliver toxins to cancer cells.

The staff started working on two simultaneous projects, preventing pregnancy and curing cancer. They are currently looking into whether other cancers — such as colon, lung, lymphomas and sarcomas — produce the protein.

The finding and the team’s continued research has attracted the interest of cancer surgeons, at least one of whom had delivered specimens of cancer tissues directly to the laboratory for testing.

“The research opens a new field of inquiry termed cancer-oocyte neoantigens and reveals a previously little known fundamental aspect of cancer — that many types of cancer, when they dysregulate or go awry, revert back and take on features of the egg, the original cell from which all the tissues in the body derive,” Herr said.

That’s important because researchers can use the protein as a target for cellular depth charges designed to destroy a cancer cell from inside.

By mixing a cancer-fighting drug with an antibody designed to attach itself to that particular protein — called a monoclonal antibody — they are able to deliver the drug directly to the cell.

“You add a SAS1B-targeted antibody with a drug on it and within 15 minutes of contacting the cancer cells, the antibody binds at the cell surface,” Herr said.

That brings the antibody bomb inside the cell. A change in surrounding acidity releases the chemical bond between the antibody and the drug, freeing the toxic payload. The drug begins to attack the malignant cell from inside, leading to cell death within a few days.

Because the antibody is designed to attach itself to only the SAS1B protein, only those cells with it are affected.

“We think we have a way not only to more specifically target cancer cells, but a way that could become a frontline treatment for women who have cancers of many types and want to preserve fertility,” Herr said.

The targeted drug delivery could mean a dramatic reduction in side effects of traditional cancer treatment such as hair loss, nausea, anemia and neuropathy, and both women and men can use the treatment. Impacts on a woman’s fertility would reverse themselves in about 200 days, the researchers say.

There is more work to be done, the researchers say. The question of why some cancer cells have the protein has not been answered, and the research team is developing a way to find tiny amounts of free-circulating SAS1B proteins in the body as a cancer detection method, Pires said.

“It could be a valuable discovery in terms of prerequisite testing to identify those patients who have tumors making SAS1B,” he said. “If everything goes well, less than a year from now we will know if we’re ready to propose a study for testing within select human populations.”

Bryan McKenzie is a reporter for The Daily Progress. Contact him at (434) 978-7271, bmckenzie@dailyprogress.com, or @BK_McKenzie.