Nathaniel Jones, M.D., intends to use findings about DNA damage to see whether there is a correlation between damage and survival rates in endometrial cancer patients. He also wants to determine whether patients with significant DNA damage are more responsive to immunotherapy.
By Carol McPhail
As a gynecologic oncologist, Nathaniel Jones, M.D., treats women suffering from endometrial cancer at the USA Health Mitchell Cancer Institute. As a physician-scientist, Jones wants to know why Black women have worse outcomes from the disease, the most common gynecologic cancer in women in the United States, and what can be done to improve their odds.
Despite recent advancements in care, Black women are 60 percent more likely to die from endometrial cancer -- a cancer that develops in the uterus -- compared with women of other races.
As an assistant professor of gynecologic oncology, Jones is beginning a research project to address this difference in Black women. His research will use a new method developed at the MCI to measure DNA damage in the tumors of endometrial cancer patients and determine whether DNA repair defects can predict how patients will respond to immunotherapy. The research is being funded by a two-year mentored grant from the National Institutes of Health.
“Ultimately, I hope our work helps change the way we triage endometrial cancer patients who come to us for treatment,” Jones said. “We have a large population of Black women who we treat here, and it is difficult knowing that they will have worse outcomes compared with white women receiving the same treatment. This research really hits close to home for us.”
Jones proposes to use the Repair Assisted Damage Detection (RADD), a new method of assessing DNA damage in tumor tissue that was developed by cancer researcher Natalie Gassman, Ph.D., assistant professor of physiology and cell biology at the University of South Alabama College of Medicine.
The RADD method harnesses the specificity of DNA repair enzymes to detect and remove DNA damage, then tags the damage sites with a fluorescent dye to allow for quantification of damage levels on a single cell level. RADD characterizes the unrepaired DNA damage left behind by defective repair machinery to understand the impact of DNA repair defects in cells and in the tumor. The technique can even be employed rapidly by pathology labs, with DNA damage measurements made within 24 hours.
“There is no comparable technology available that can assess DNA damage within tissue samples,” Jones said.
He intends to use findings about DNA damage to see whether there is a correlation between damage and survival rates in endometrial cancer patients. He also wants to determine whether patients with significant DNA damage are more responsive to immunotherapy. Immunotherapy is a type of cancer treatment that boosts the body’s natural defenses to find and destroy cancer cells.
The technique will allow DNA damage to be assessed on individual patients’ tumors so that physicians can make better informed decisions about treatment, such as prescribing immunotherapy prior to the standard regimen of chemotherapy.
Jones wants to take the research a step further by measuring the immune response to therapy among Black women with various percentages of African American genetic makeup. “The study will strive to more completely understand the relationship between DNA damage levels, therapeutic response and disease outcomes for patients stratified by the genetic definition of race,” he said. “We intend to provide a novel perspective on uterine cancer health disparities and create models for personalized medicine for minority populations.”
MCI operates the largest gynecologic oncology practice in the upper Gulf Coast region and has a reputation for impactful research into cancer health disparities, said Rodney Rocconi, M.D., the Elsie Colle Chair of Oncology Research and associate director for clinical research and professor of gynecologic oncology at the MCI.
“Despite the focus to improve cancer outcomes in people of color, unfortunately, our Deep South region has some of the worst cancer inequities in the country,” said Rocconi, who will serve as mentor to Jones for the research project. “Our prior work has shown that when controlling for social and treatment factors, even within clinical trials, that a worse survival still exists for Black patients with uterine cancers, including endometrial cancer. This project should improve the treatment for Black women with endometrial cancer and hopefully close the survival gap, so that more women can live longer, healthier lives.”