Researchers identify “master regulator” gene that could lead to more effective treatment for patients with ovarian cancer

Two cancer drugs increase the expression of a potential biomarker that correlates with improved survival outcomes in patients with treatment-resistant ovarian cancer.

In a study co-led by the University of Maryland School of Medicine (UMSOM), researchers have identified a “master regulator” gene, ZNFX1, that may act as a biomarker to help guide treatment in future clinical trials involving patients with therapy-resistant ovarian cancer, according to a study recently published in Cancer Research.

A group of researchers from several institutions, including the University of Maryland School of Medicine (UMSOM), Indiana University School of Medicine-Bloomington, and the Johns Hopkins University School of Medicine, looked at patient ovarian cancer databases and found that high levels of ZNFX1 correlate with how patients with advanced stage disease will respond to certain therapies, making it a potential predictor of therapy responses. ZNFX1 also correlated with an increase in overall survival in a previously conducted phase three clinical trial where patients received the cancer drug bevacizumab in combination with chemotherapy. In addition, the study showed that two cancer drugs, DNA methyltransferase inhibitors (DNMTi) and PARP inhibitors, increase the expression of ZNFX1 and serve as a gateway to tumor suppressing inflammatory responses in cancer cells.

“ZNFX1 may serve as a biomarker to facilitate more personalized therapy in ovarian cancer patients,” said senior author, Feyruz V. Rassool, PhD, professor of radiation oncology at UMSOM and co-director of the experimental therapeutics program at the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC). “Our findings build upon our previous research into DNMTi and PARP inhibitors to find potential uses for these drugs in treating different forms of cancer.”

Taofeek K. Owonikoko, MD, PhD, UMGCCC’s Executive Director and the Marlene and Stewart Greenebaum Distinguished Professor of Oncology at UMSOM, said, “The identification of ZNFX1 as a potential biomarker in ovarian cancer treatment offers a path forward for further research in a clinical setting. UMGCCC is committed to advancing new therapies and bringing forward scientific discoveries that have the potential to improve outcomes for patients.”

This research was funded by grants from a number of organizations, including the Adelson Medical research foundation, the Van Andel Institute Stand Up to Cancer Epigenetics Dream Team, and a Specialized Program of Research Excellence (SPORE) grant through the National Cancer Institute (NCI) awarded to The Coriell institute for Medical Research and Van Andel Institute in 2021. Dr. Rassool, Ken Nephew, PhD with the Indiana University Melvin and Bren Simon Comprehensive Cancer Center and Stephen B. Baylin, MD with The Sidney Kimmel Comprehensive Care Center at Johns Hopkins are among nearly 20 scientists at six institutions working to improve epigenetic therapies for cancer with the five-year, estimated $12.4 million SPORE grant.

About the University of Maryland School of Medicine

Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world -- with 46 academic departments, centers, institutes, and programs, and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1.2 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically based care for nearly 2 million patients each year. The School of Medicine has nearly $600 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 students, trainees, residents, and fellows. The combined School of Medicine and Medical System ("University of Maryland Medicine") has an annual budget of over $6 billion and an economic impact of nearly $20 billion on the state and local community. The School of Medicine, which ranks as the 8th highest among public medical schools in research productivity (according to the Association of American Medical Colleges profile) is an innovator in translational medicine, with 606 active patents and 52 start-up companies. In the latest U.S. News & World Report ranking of the Best Medical Schools, published in 2023, the UM School of Medicine is ranked #10 among the 92 public medical schools in the U.S., and in the top 16 percent (#32) of all 192 public and private U.S. medical schools. The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu

About the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center

The University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center is a National Cancer Institute-designated comprehensive cancer center within the University of Maryland Medical Center in Baltimore, the flagship academic hospital of the University of Maryland Medical System. It offers a multidisciplinary approach to treating all types of cancer and has an active clinical and basic science research program through its relationship with the University of Maryland School of Medicine. The center is ranked among the top 50 cancer programs in the country by US News & World Report. www.umgccc.org