New chemotherapy drug that is gentle on fertility but tough on cancer
Washington, Mar 23 : A new gentler chemotherapy drug in the form of nanoparticles has been designed by scientists 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 Northwestern Medicine scientists designed a quick new in vitro test that predicts the toxicity of a chemotherapy drug to fertility and 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," Teresa Woodruff, a co-principal investigator of the study and chief of fertility preservation at Northwestern University Feinberg School of Medicine said.
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.
Woodruff and Thomas O'Halloran, also a co-principal investigator and director of the Chemistry of Life Processes Institute at Northwestern, are a wife and husband team who developed and tested the drug.
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," O'Halloran said.
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.
Arsenic trioxide was approved a few years ago for treating some types of blood cancers such as leukemia in humans, but O'Halloran thinks the arsenic trioxide nanobins can be used against breast cancer and other solid tumors.
In his previously published preclinical research, nanobins were effective in reducing tumor growth in triple-negative breast cancer, which often doesn't respond well to traditional chemotherapy and has a poor survival rate.
The research is published in the journal PLOS ONE.