An iron-binding medication that is already approved for use in treating other health issues might offer a fresh strategy for tackling ovarian tumors, according to a recent study. This preclinical research merged the examination of human ovarian tumors with animal models of the disease.
According to a new study led by researchers from Weill Cornell Medicine, an iron-binding drug already sanctioned for other medical ailments could provide a new method for combating ovarian tumors. This preclinical research, which integrated the analysis of human ovarian tumors and animal models, was featured in the journal Cancer Discovery published on July 29 by the American Association for Cancer Research.
The body requires iron for various cellular activities, and cancer cells that replicate quickly often require more iron than typical cells. This is particularly true for ovarian cancers.
“This presents an excellent opportunity for exploring a new treatment method using an FDA-approved iron-chelating drug called deferiprone, which has shown success in treating other conditions with abnormal iron buildup,” stated Dr. Juan Cubillos-Ruiz, the senior author and a distinguished associate professor at Weill Cornell Medicine. Iron-chelating medications attach firmly to iron, thus hindering cells from utilizing it.
To substantiate the role of iron in ovarian cancer, Dr. Cubillos-Ruiz’s team initially examined a compilation of human tumor samples they’ve gathered over the last decade and analyzed public genomic datasets from ovarian cancer patients in collaboration with an international team.
“We are capable of isolating various components of tumors from ovarian cancer patients, allowing us to investigate their molecular functions,” noted Dr. Cubillos-Ruiz, who also co-leads the Cancer Biology Program at the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.
The researchers discovered that ovarian cancer cells show heightened expression of genes linked to iron, which correlated with worse outcomes for patients. They also identified that the fluid around ovarian tumors contained a high amount of iron accessible to cancer cells.
Next, the team evaluated animal models of the disease.
“We have developed mouse models of metastatic ovarian cancer that are immunocompetent, enabling us to observe the immune system’s response within the disease context, which is crucial,” explained Dr. Cubillos-Ruiz. Prior investigations related to iron had used mice with weakened immune systems, limiting comprehension of how various therapies impact immune responses to tumors.
The team found that the mice reflected the disease characteristics effectively: as ovarian cancer advanced, there was increased iron accumulation in the tumor, and the cancer cells displayed selective overexpression of iron-related gene profiles.
In these models, treatment with deferiprone proved even more effective than cisplatin, the conventional chemotherapy for ovarian cancer, operating directly within the cells. “We demonstrated that deferiprone can chelate iron in ovarian cancer cells in vivo,” stated Dr. Tito Sandoval, the lead author and former postdoctoral fellow in Dr. Cubillos-Ruiz’s lab.
“We discovered that the combination of cisplatin and deferiprone significantly prolonged the survival of mice with metastatic ovarian cancer, working synergistically in comparison to each drug alone,” said Dr. Sandoval, now a senior scientist in radiation oncology at Washington University School of Medicine in St. Louis. “We then aimed to determine the mechanisms behind this interaction.”
The team found that by depriving cancer cells of iron, deferiprone triggers a stress response in the cells, which activates the immune system to attack them. Since cisplatin works on the DNA replication of cancer cells, it appears that both drugs complement each other well.
Dr. Cubillos-Ruiz is currently collaborating with clinical partners to formulate human trials centered around this new treatment approach. Even though deferiprone is already approved for other uses, he emphasized the need to determine the most effective application against ovarian cancer. “We aim to optimize the potential therapeutic benefits, making the trial design essential,” he remarked.
