Southern Research scientists target mutated protein to combat prostate cancer

Southern Research scientists are exploring how a mutated protein implicated in prostate cancer plays a role in the development of the disease and whether it holds a key to better treatment outcomes.

The research focuses on a protein called SPOP and how its mutated form interacts with the DNA damage response, a network of cellular pathways that works non-stop in an attempt to repair damaged DNA strands and prevent potentially harmful changes.

The findings could point to a new therapeutic target or a biomarker that predicts whether or not a certain course of treatment will deliver benefits for a prostate cancer patient, according to Dr. Bo Xu, M.D., Ph.D., Distinguished Fellow and Chair of the Oncology Department at Southern Research.

"Ideally, our hope is that these findings somehow inform physicians to better diagnose and treat patients," said Joshua Fried, a researcher working in Xu's lab. "Ultimately, that's the goal of every cancer biology researcher. They want to better inform physicians."

Fried is scheduled to make a presentation about the project on April 17 at the American Association of Cancer Research's (AACR) 2018 annual meeting in Chicago. The AACR is the largest scientific organization in the world focused on every aspect of high-quality, innovative cancer research.

'PRECISION MEDICINE'

Xu said the study is significant because prostate cancer is the most common form of malignant cancer in American men, and about 20 percent of patients have mutations in this particular protein.

"One of our goals is to understand how these mutations affect a patient's therapeutic response and to determine whether we can take advantage of these mutations as a biomarker to identify patients who are more likely to benefit from radiation or chemotherapy," Xu said.

Additionally, the Southern Research team is trying to determine whether the mutation's interactions with other proteins could expose how to boost the effectiveness of radiation and chemotherapy for patients with non-mutated SPOP, he said.

"We might be able to target that interaction to mimic the mutation so the patient would benefit more from the treatment," Xu said.

"This is precision medicine, precision oncology, based on genetic information."

DNA DAMAGE RESPONSE

Fried said SPOP – just one of several mutations associated with prostate cancer – caught the attention of the Southern Research team because evidence showed that prostate cancer cells with mutated SPOP had increased chromosomal gains and losses compared to tumors without it.

"That led us to believe that there could be some involvement in the DNA damage response, and that is where our expertise is," said Fried, a postgraduate student in cancer biology at the University of Alabama at Birmingham who has been working on the project for four years.

Despite advances, progress is needed against prostate cancer.

An estimated 165,000 new cases of prostate cancer are diagnosed in the U.S. each year, according to the American Cancer Society. The disease is responsible for around 30,000 deaths annually, making it the second leading cause of cancer death in American men.

Fried said physicians and prostate cancer patients could benefit from a biomarker based on the SPOP mutation that better directs the course of treatment.

Androgen-deprivation therapy, for example, is currently part of the front-line treatment of prostate cancer, he said. But hormone therapy can have undesirable side effects and doesn't work for all patients.

"You want to spare patients treatments that are less than efficacious and streamline them into the ones that you know are going to work best," Fried said. "Chemotherapy and radiation can be tough, so if we can spare patients from one seeming unnecessary treatment, that would be better."