Cisplatin and its impact on female fertility

Researchers from Italy say they have identified a mechanism by which chemotherapy can make a woman lose her chances of having children.

Curiously, scientists also discovered that another anti-cancer drug could counteract the negative symptoms of the chemotherapy drug, cisplatin.

The discovery, demonstrated in mice and reported online in Nature Medicine, raises hopes for a way to protect a woman's fertility while on treatment for cancer but, the study authors stress, may still be completely wrong.

"The extension of these findings to patients and designing clinical trials is likely to require the development of targeted drug delivery strategies to prevent any potential interference with anti-cancer therapy systems," explained study author Stefania Gonfloni, from the biology department at the University of Rome.

"I think it's a great idea. They found a pathway that can be used as a marker to detect which drugs will result in cells dying as a result of chemotherapy, and they found a drug that has a remedial effect," said Dr. George Attia, an associate professor of reproductive endocrinology and infertility at the University of Miami Miller School of Medicine. "But this is very basic scientific research. It is still preliminary."

Because chemotherapy affects the egg cells in the ovaries, women usually end up with ovarian failure and infertility as a result of cancer treatment.

"We often work with women who are of reproductive age, and there is a lot of concern about maintaining fertility even in older women, chemo causes menopause." said dr. Igor Astsaturov, an assistant professor of medical oncology at Fox Chase Cancer Center in Philadelphia. "The current standard approach is to retrieve the eggs for storage and use at a later date."

Chemotherapy can also cause genetic defects in offspring. In particular, cisplatin, which was studied in this study, causes damage to certain types of chromosomes. Cisplatin is commonly used in treating uterine cancer, notes Attia.

In this study, Gonfloni and co-workers showed that cisplatin causes the death of oocytes or germ cells in women, originating from the enzyme c-Abl, a protein that, when mutated, can also cause chronic myeloid leukemia (CML).

But targeting the enzyme with imatinib (Gleevec), a drug used to treat CML, protects oocytes from the deleterious effects of cisplatin.

"These results raise the possibility of protecting ovarian function during cancer treatment, thereby preserving the fertility of women who have survived cancer," said Gonfloni.

But how to use one drug without harming the other?

"First, we have to show that imatinib can be used to prevent chemotherapy-induced ovarian toxicity without interfering with anti-cancer medication." Gonfloni said. "In other words, we have to prove that laboratory animals with tumors can be cured by the combination of cisplating and imatinib treatment, while at the same time, preserving fertility," he explained.

"Then, for any clinical implications, it will be very important to prove the same protective effect of a certain dose of imtinib in human oocytes maintained and challenged with chemotherapy drugs in vitro," he added.

And fertility maintenance isn't always the right thing, says Astsaturov. "Chemotherapy causes menopause for some cancer patients who are dependent on several hormones . This is a beneficial effect because it removes stimulants for cancer cells . Menopause is a contribution to recovery," he said. "It is debatable whether we should maintain menstrual function in any way."

From MedicalEra