Portage County Legal News

OSU researchers study breast cancer drug's paradoxical effects

KEITH ARNOLD
Special to the Legal News
Published: August 22, 2017

Ohio State University researchers examined what they characterize as a cascade of events that lead to metastatic breast cancer in which a leading chemotherapy drug is partly responsible for the further spread of the disease.

Researchers found that the chemotherapy drug paclitaxel sets off a variety of molecular-level changes that allow breast cancer cells to escape from the tumor, at the same time creating an environment in the lung that is more hospitable to those cells, the study found.

"That chemotherapy can paradoxically promote cancer progression is an emerging revelation in cancer research. However, a molecular-level understanding of this devastating effect is not clear," said Tsonwin Hai, the study's senior author and a professor of biological chemistry and pharmacology.

The study appears in the journal Proceedings of the National Academy of Sciences, according to a university press release.

It includes an analysis of data from women with breast cancer that suggest the findings from mouse models could be relevant to breast cancer metastasis in humans.

The changes in both the tumor and the lung documented in the study depend on a gene called Atf3, which is turned on by stress, researchers found.

In human data, the study found higher Atf3 gene expression in patients who had chemotherapy than those who did not.

"This gene seems to do two things at once: Essentially help distribute the 'seeds' (cancer cells) and fertilize the 'soil' (the lung)," she said.

The chemo appears, initially, to send signals to increase the number of molecular doors through which the cancer cells can escape from the primary tumor into the bloodstream, freeing them to travel to other organs, the researchers found.

"I think it's an active process - a biological change in which the cancer cells are beckoned to escape into the blood - rather than a passive process in which the cancer cells get into the bloodstream because of leaky vessels," said Hai, a member of The Ohio State University Comprehensive Cancer Center.

The study reasoned that beyond aiding cancer cell escape, paclitaxel creates a cascade of events that making the tissue environment in the lung fertile ground for circulating cancer cells.

"There are signals that help cancer cells enter the lungs and set up shop, that make the environment more immunologically tolerant to cancer cells," she said.

Ohio State researchers Yi Seok Chang, Swati Jalgaonkar and Justin Middleton joined Hai to work on the study.

The U.S. Department of Defense supported the study.

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