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Scientists Discover How Chemo Can Make Women Infertile
Date:9/28/2009

But drug Gleevec counteracted effect in mouse study

MONDAY, Sept. 28 (HealthDay News) -- Italian researchers say they have identified the mechanism by which chemotherapy can rob a woman of her ability to have children.

Intriguingly, the scientists also found that another anti-cancer drug might counteract the negative effects of the chemotherapy drug cisplatin.

The finding, demonstrated in mice and reported in the Sept. 27 online edition of Nature Medicine, raises the hope that there might be a way to protect a woman's fertility while she undergoes treatment for cancer but, the authors stressed, this is still a long way off.

"The extension of these findings to patients and the design of clinical trials is likely to require the development of targeted drug delivery strategies to avoid any potential interference with anti-cancer systemic therapy," explained study author Stefania Gonfloni, of the department of biology 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 drug would produce cell death as a result of chemotherapy, and they found a repair effect of a drug," said Dr. George Attia, an associate professor of reproductive endocrinology and infertility at the University of Miami Miller School of Medicine. "[But] it's very basic science research. It's still early."

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

"We frequently deal with women of childbearing age, and there's a lot of concern about fertility preservation although as women get older, the chemo induces menopause," said Dr. Igor Astsaturov, an assistant professor of medical oncology at Fox Chase Cancer Center in Philadelphia. "The standard approach now is egg collection [storing eggs for later use]."

Chemotherapy can also cause genetic defects in offspring. In particular, cisplatin, which was studied in this trial, causes specific types of chromosomal damage.

Cisplatin is primarily usually used to treat ovarian cancer, Attia noted.

In this study, Gonfloni and her colleagues showed that cisplatin promotes the death of oocytes, or female germ cells, by way of the c-Abl enzyme, 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, protected the oocytes from the ill effects of cisplatin.

"These results raise the possibility of protecting ovarian function during cancer treatments, thereby preserving the fertility in female cancer survivors," Gonfloni added.

But how to use one drug without compromising the other?

"First, we have to show that imatinib can be used to prevent chemotherapy-induced ovarian toxicity without interfering with anti-cancer treatments," Gonfloni said. "In other words, we have to prove that tumor-bearing laboratory animals can be cured with a combined cisplatin and imatinib treatment, while at the same time preserving fertility," she explained.

"Then, for any clinical implications, it will be very important to prove the same protective effect of a specific dosage of imatinib on human oocytes cultured and challenged with chemotherapeutic drugs in vitro," she added.

And preserving fertility is not always the right thing, Astsaturov said.

"Chemotherapy induces menopause in some hormone-dependent cancers. It has a beneficial effect because it's withdrawing the stimulants for the cancer cells. Menopause is contributing to the cure," he said. "It's still debated whether we should preserve menstrual function at all costs."

More information

Visit Cancer Research UK for more on chemotherapy and fertility.



SOURCES: Stefania Gonfloni, Ph.D., department of biology, University of Rome, Italy; George Attia, M.D., associate professor, reproductive endocrinology and infertility, University of Miami Miller School of Medicine; Igor Astsaturov, M.D., assistant professor, medical oncology, Fox Chase Cancer Center, Philadelphia; Sept. 27, 2009, Nature Medicine, online


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