ZNFX1

In a study co-led by the Indiana University Melvin and Bren Simon Comprehensive Cancer Center, researchers have identified a “master regulator” gene called ZNFX1. This gene may act as a biomarker to help guide treatment in future clinical trials involving patients with therapy-resistant ovarian cancer. The study was published in this month’s print edition of the journal Cancer Research.

A group of researchers from several institutions 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. In addition to IU, the study was led by researchers from the University of Maryland School of Medicine (UMSOM) and Johns Hopkins University School of Medicine.

“This study really is a cooperative effort to understand this novel gene and its role in responses to immunotherapies,” Ken Nephew, PhD, co-corresponding author, said. “The response to immunotherapy in ovarian cancer patients has been quite modest; our study of ZNFX1 could help us understand why that is and could potentially be a mechanism to improve responses to immunotherapy.”

Nephew is the Jerry W. and Peggy S. Throgmartin Professor of Oncology at the IU Simon Comprehensive Cancer Center and IU School of Medicine, Bloomington. Nephew and Kathy Miller, MD, Ballvé Lantero Professor of Oncology, co-led the IU efforts for the study.

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. “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.”

This research was funded by grants from a number of organizations, including a Specialized Program of Research Excellence (SPORE) grant through the National Cancer Institute awarded to The Coriell institute for Medical Research and Van Andel Institute in 2021. Nephew and Miller 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.