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However, these failures provided a critical insight that would eventually lead to a groundbreaking discovery. “The drug failed in the hot flash studies in a very particular way,” said McDonnell, Glaxo-Wellcome Distinguished Professor of Molecular Cancer Biology. “It worked at very low doses, and as you increased the dose, it actually made the hot flashes worse.”

This peculiar behavior intrigued McDonnell and his team. In 2012, two lab members — Suzanne Wardell, today an assistant professor working in McDonnell's lab, and Erik Nelson, now a faculty member at the University of Illinois — were fascinated by the drug's inverted U-shaped dose-response curve. This anomaly suggested that the drug might have potential for a completely different use than for hot flashes. “We had been exploring some biology that made us think that this drug, for the very reason it failed, might make it an outstanding breast cancer drug,” McDonnell said.

Very soon thereafter, the lab reported findings that the drug reduced the expression of the estrogen receptor in breast cancer cells and inhibited the growth of estrogen-receptor- positive tumors in mice. The team filed for patents for use of the drug in fighting breast cancer and convinced the drug owners, Radius Health, Inc., to bring the repurposed drug to clinical trials for breast cancer.

Elacestrant targets a specific type of breast cancer resulting from mutations in an estrogen receptor called ESR1. This type of cancer is found in about 40% of advanced or metastatic breast cancers that register positive for the estrogen receptor.

Before elacestrant, patients such as Mei were unable to use standard endocrine therapy. Now thousands of women around the world are using the drug in its first two years of being on market.

How it works is simple, McDonnell said. In this type of breast cancer, estrogen is central to tumor growth. Elacestrant blocks the estrogen receptor. No receptor, no cancer growth.

“What our drug does is it twists the receptor into a shape that the cell recognizes as broken or defective,” McDonnell said. “In essence it shuttles it to the trash can. Within four hours, the receptor is gone. It's very quick.”

Why it works so well is less simple. “We don't understand,” McDonnell said. “This is exciting, because it means there is more research we need to do. Understanding how it works is helping us to develop the next generation of drugs that target the estrogen receptor.  In fact a second drug that came from this research, lasofoxifene, is now in late stage clinical trials.”

Lasofoxifene has a side effect, but a positive one, reducing incontinence by blocking estrogen from affecting the pelvic and bladder muscles, improving the quality of life of the patient. It also prevents bone loss generally associated with the use of endocrine therapies for breast cancer.

“I’ll tell you my goal,” said McDonnell, leaning forward. “My goal is to change the conversation in oncologists’ office from, ‘Mrs. Jones, we can treat your cancer’ to ‘We can cure you of your cancer.’

“There are going to be steps along the way that should not be changed. And one of those steps is to be able to say, ‘Mrs. Jones, we can treat your cancer and add to your quality of life rather than detract from it.’”

But the future all depends on federal funding. The collaboration between the federal government and research universities is already highly selective; only around 9% of cancer research grant applications are approved on the first round. McDonnell said putting significant restrictions on these already difficult to secure grants would endanger critical research.

“The biomedical research engine in the United States right now is one of the strongest in the world,” he said. “Efficiency is inherently built into the system because we are picking the absolute best shots on goal every time. It’s already a challenge to distinguish between the top 20% of grants because they're all so good. If we further reduce funding, we’re talking about less breakthrough research, we're talking about cuts to clinical trials and about cuts to training programs for the next generation of researchers.”

Federal funding also enables universities to engage in long-term research. McDonnell, who has worked in private industry, said it’s that ability to engage in high-risk, high-return research -- and the time it takes to turn failure into success -- that attracted him and other top researchers to do research in an academic setting.

McDonnell recalled a speech he gave to a group of businessmen in which he described the long journey of drug discovery. Afterward, a businessman in the oil industry spoke to him: “You'd never survive in my business, because if we drilled for 20 years and didn't find oil, we'd be out of business,” the man said.

“The reason that I came from industry to academics was because the life cycle of projects in private industry is too short for me,” McDonnell said. “I need a longer reign, a longer leash.”

At her home, Mei said she’s a believer.” We need that research to improve the lives of patients. Without this research, we won’t have the advances that got me the help I needed.”

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