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.
Feyruz V. Rassool, PhD
“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.