New chemotherapy drug is gentler on fertility yet tougher on ovarian cancer

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A new gentler chemotherapy drug in the form of nanoparticles has been designed to be less toxic to a young woman's fertility but extra tough on cancer. This is the first cancer drug tested while in development for its effect on fertility using a novel in vitro test.

The scientists involved designed a quick new in vitro test that predicts the toxicity of a chemotherapy drug to fertility and that can be easily used to test other cancer drugs in development as well as existing ones. Currently the testing of cancer drugs for fertility toxicity is a time- and resource-intensive process.

"Our overall goal is to create smart drugs that kill the cancer but don't cause sterility in young women," said Teresa Woodruff, PhD, a coprincipal investigator of the study and chief of fertility preservation at Northwestern University Feinberg School of Medicine. The paper was published in PLOS ONE (2013; doi:10.1371/journal.pone.0058491).

The scientists hope their integration of drug development and reproductive toxicity testing is the beginning of a new era in which chemotherapy drugs are developed with an eye on their fertotoxity (fertility toxicity). As cancer survival rates increase, the effect of cancer treatments on fertility is critically important to many young patients.

The chemotherapy drug, arsenic trioxide, is packed into a very tiny Trojan horse called a nanobin. The nanobin consists of nano-size crystalline arsenic particles densely packed and encapsulated in a fat bubble. The fat bubble, a liposome, disguises the deadly cargo—half a million drug molecules.

"You have to wallop the tumor with a significant dose of arsenic but at the same time prevent exposure to normal tissue from the drug," said coauthor Thomas V. O'Halloran, PhD. The fat bubble is hundreds of times smaller than the average human cell. It is the perfect size to stealthily slip through holes in the leaky blood vessels that rapidly grow to feed tumors. The local environment of the tumor is often slightly acid; it is this acid that causes the nanobin to release its drug cargo and deliver a highly effective dose of arsenic where it is needed.

The scientists show this approach to packaging and delivering the active drug has the desired effect on the tumor cells but prevents damage to ovarian tissue, follicles, or eggs.

While the drug is gentle on fertility, it is ferocious on cancer. When tested against lymphoma, it was more potent than the drug in its traditional free form.

"The drug was designed to maximize its effectiveness but reduce fertotoxicity," said O'Halloran, also the Morrison Professor of Chemistry in the Weinberg College of Arts and Sciences at Northwestern. "Many cancer drugs cause sterilization, that's why the reproductive tract is really important to focus on in the new stages of drug design. Other body systems get better when people stop taking the drug, but fertility you can't recover."

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