Protein Identified as Potential Drug Target for Cancer Treatment

Novel method may reduce the length of treatment time and decrease side effects.

Researchers at the University of Virginia School of Medicine have discovered a new strategy for attacking cancer cells that could alter the way physicians treat and prevent the disease.

By more selectively targeting cancer cells, the method offers a way to reduce the length of time of treatment as well as the side effects associated with current treatments.

“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,” said reproduction researcher John Herr, PhD, of UVA’s Department of Cell Biology.

Herr and research partner Eusebio Pires, PhD specialize in germ cells, the reproductive cells that make up sperm and eggs. As they researched possible new methods of contraception, the team discovered a link between developing eggs and tumors. The discovery will allow scientists to use antibodies to deliver medication directly to tumors without harming healthy cells.

Herr and Pires made the discovery while studying a protein called SAS1B, which is typically only on the surface of developing and mature egg cells.

“Except for the small group of growing eggs in the ovary, the SAS1B protein is virtually absent in other tissues in the body,” Pires said. “So SAS1B has the promising features of a candidate contraceptive target.”

The restriction of SAS1B to growing eggs suggests strategies for developing improved female contraceptives that selectively target only the pool of growing eggs, potentially reducing unwanted side effects of current steroidal contraceptives.

While the experiment started by focusing on SAS1B because of its potential in contraception, a sample that showed expression of the protein in a uterine cancer led scientists to test if it were present in other cancer types. Thus far, the team has discovered SAS1B expression in breast, melanoma, uterine, renal, ovarian, head and neck, and pancreatic cancers. There is also evidence to suggest that it appears in bladder cancers.

“The research opens a new field of enquiry, 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 explained.

Herr and Pires have used this information to develop a method for delivering medication using SAS1B protein as a target.

SAS1B protein appears only in cancer cells and egg cells, making it a good target for tiny tracking probes created using monoclonal antibodies. Monoclonal antibodies are highly pure antibodies designed to bind to one single target protein with a uniform affinity.

The antibodies bind to any cell that possessed SAS1B protein. They then act as tiny injectors for targeted medication.

“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 and the antibody-SAS1B complexes begin the internalization process,” Herr said.

After an hour of entering the body, the antibody-SAS1B complexes release their toxic drugs, triggering changes leading to cell death within a few days.

This targeted method could mean a significant reduction in treatment-related side effects compared with traditional cancer therapies. The method also reduces the chance of harm to normal, healthy cells. For female cancer patients especially, a drug that doesn’t touch their body’s reserve of quiescent eggs could be a huge breakthrough.

The monoclonal antibodies would only attach to growing egg cells and SAS1B positive cancer cells, leaving the ovaries’ supply of dormant eggs untouched. This would mean that normal ovulation could continue once treatment is complete and oocytes are again recruited to develop and ovulate, which takes approximately 200 days.

In addition to treating cancer, this new method could also lead to early cancer detection and prevention. The research team is currently trying to find a way to detect tiny amounts of free-circulating SAS1B proteins in the body, according to Pires.

“It could be a valuable discovery in terms of prerequisite testing to identify those patients who have tumors making SAS1B,” he said.

It is the hope of scientists that physicians will one day be able to use the monoclonal antibodies to detect SAS1B levels in patients’ blood. Those whose test results come back with high levels of the protein could be tested for early stage cancer and receive treatment earlier.

As they refine the method, Herr and Pires plan to begin testing the treatment in model organisms that carry human tumors at UVA’s labs in the fall.

“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,” Pires said.