Preserving Fertility During Chemotherapy Using Available Cancer Drug

Everolimus, a drug used to slow tumor growth, could prevent chemotherapy-induced infertility, according to researchers at NYU Langone Medical Center. In a paper published in the journal, Proceedings of the National Academy of Sciences, the researchers detail how the drug provides a protective effect on the ovaries during chemotherapy.

The researchers tested the drug in mice who were given cyclophosphamide, a chemotherapy agent commonly used to treat breast cancer. While cyclophosphamide can be effective, it has the undesirable side effect of depleting egg cells in the ovaries, thereby reducing future fertility.

Female mice treated with chemotherapy alongside everolimus were found to have two times the number of offspring, compared to mice given cyclophosphamide alone. According to the study authors, these encouraging preclinical results could quickly push the drug into clinical trials involving female cancer patients.

“Our results argue that everolimus may represent a fertility-sparing drug treatment to complement the freezing of eggs and embryos, which are valued methods, but time-consuming, costly, less effective with age, and not protective of long-term ovarian function,” said lead author, Dr. Kara Goldman, reproductive endocrinologist at NYU Langone. “Patients, including young girls, face devastating choices as they try to balance cancer treatment against their ability to have children in the future. We need more options.”

Along with testing everolimus in the mice, the researchers also studied an experimental drug, known as INK128. Both drugs slow tumor growth by inhibiting the actions of the enzyme, mTOR, which is involved in pro-cell growth signaling mechanisms.

Cyclophosphamide belongs to a class of drugs known as alkylating chemotherapies, which targets and damages the DNA of rapidly growing cancer cells. This drug has also been found to promote mTOR, thereby speeding maturation and multiplication of ovarian follicles. Cyclophosphamide then targets these egg cells and damages their DNA, causing cell death of many of these cells.

To try to counteract this damaging effect on fertility, the researchers sought out to determine whether currently-available mTOR inhibitors could block this side effect of chemotherapy. On average, mice treated with chemotherapy and one of the mTOR inhibitors had 7.4 pups; mice treated with chemotherapy had just 3.4 pups.

Mice treated with cyclophosphamide alone also showed a 64 percent reduction in the number of primordial follicles, which could be prevented using mTOR inhibitors. In addition to its use in preventing fertility problems in women being treated with chemotherapy, everolimus might also have potential in extending reproductive lifespan in women who experience early menopause.

“Only clinical trial results will tell whether these drugs can protect fertility and counter hormonal deficits naturally by preserving follicles,” said senior author Dr. Robert Schneider, the Albert B. Sabin Professor of Molecular Pathogenesis and associate dean for Biomedical Innovation at NYU Langone. “Our goal is to complete studies on the best dose for ovarian preservation, and then to get everolimus into a trial for this use next year.”