An existing drug may improve ovarian cancer treatment

Ovarian cancer cells with activated Notch3 are more sensitive to auranofin. A, Western blot analysis of total cell lysates showing Notch3 and RBPJ levels in seven established ovarian cancer cell lines. Histone H3 was used as a loading control. B, Summary of IC50 values for auranofin in the seven ovarian cancer cell lines tested, shown as means ± SEM. C, Representative examples of auranofin dose-response curves in the ovarian cancer cell lines tested. Cells were treated with varying concentrations of auranofin for 72 hours. Cell viability was determined using the ATP-Glo Bioluminometric Cell Viability Assay. IC50 values were determined by fitting the data points using the four-parameter sigmoidal model. Credit: Cancer Research Communications (2025). DOI: 10.1158/2767-9764.crc-25-0190

Hua-Ying Fan, PhD, hopes that her team’s latest discovery could help the almost 21,000 people who are expected to receive an ovarian cancer diagnosis this year.

Fan’s team at The University of New Mexico Comprehensive Cancer Center discovered that a drug approved by the US Food and Drug Administration (FDA) may sensitize ovarian cancer cells to standard chemotherapy treatment. Their work is published in Cancer Research Communications.

Ovarian cancer is often caught in later stages, and no screening tests are available for it. The National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) program predicts that 20,890 people will receive an ovarian cancer diagnosis and 12,730 will die from the disease in 2025.

Current treatments and their limitations

Standard treatment for ovarian cancer starts with a platinum-based chemotherapy, such as carboplatin or cisplatin. This chemotherapy is often given with another drug called paclitaxel. More than 80% of people with advanced ovarian cancer respond to this treatment.

But, Fan says, only half of them live longer than 18 months after diagnosis because the cancer often returns. And when it returns, the cancer cells no longer respond to cisplatin. Treatment options become limited once ovarian cancer cells become resistant to platinum-based chemotherapy.

Exploring new approaches with the Notch pathway

So in 2017, Fan decided to look for ways to help patients with recurrent ovarian cancer. Using the results from previous work, she focused on a series of cellular chemical reactions called the Notch pathway.

The Notch pathway guides how cells specialize. In one of the Notch reactions, a protein called RBPJ binds to DNA in the nucleus of the cell. This binding controls the genes that control how the cell specializes.

Fan’s previous work showed that a drug called auranofin prevents RBPJ from binding to DNA, disrupting the Notch pathway. Auranofin is approved by the FDA to treat rheumatoid arthritis.

Testing the drug combination in the lab

Fan then worked with Kimberly Leslie, MD, an expert in gynecologic cancers, who provided many ovarian cancer cells for experiments. Leslie also advised on ovarian cancer treatments.

Certain ovarian cancer cells, called OVCAR3 cells, depend on the Notch pathway for their development much more than non-cancerous cells do. OVCAR3 cells do not respond to cisplatin. But when Fan’s team treated these cells with auranofin plus cisplatin, many of them died.

Fan also worked with Mara Steinkamp, PhD, an expert in cancer organoids and animal models. Cancer organoids are three-dimensional clusters of cancer cells that are grown from the cells taken from patients. Organoids from a single patient can be used as a model of that patient’s cancer.

The team grew the organoids from tumor cells that were taken from people with ovarian cancer and then treated them with auranofin plus cisplatin. In the organoids that were treated with a greater amount of the drug combination, more ovarian cancer cells died.

The team also used small animals with ovarian tumors to study the effect of their drug combination. The animals that received greater amounts of the drugs lived longer and had fewer and smaller tumors.

Looking ahead to future studies

“This study reflects broad collaboration across clinical, translational and basic science teams at UNM Comprehensive Cancer Center,” Fan says.

But she cautions that more studies are needed before the drug combination can be given to people with advanced ovarian cancer. And because of the variation among ovarian cancer patients, not every patient may benefit from this discovery.

Still, Fan has hope that future studies will show a potential benefit for many people. For them, making their treatment a notch more effective may enable them to live beyond the average 18 months.

Transcription factor drives chemotherapy resistance in ovarian cancer