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Scientist: ‘we got some strange, early results’

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@stephchoover

As Breast Cancer Awareness Month kicks in, UNM scientist Eric Prossnitz and NMSU scientist Jeffrey Arterburn continue their ongoing fight against the disease.

Prossnitz and Arterburn have been working together for about 10 years studying a new type of estrogen receptor, which would show potential ways to treat and diagnose breast cancer.

“We studied and helped characterized … GPR30, which is a completely different type of estrogen receptor than the nuclear estrogen receptor that’s such an important characteristic for the diagnosis of what’s the best treatment of a breast cancer,” Arterburn said.

Prossnitz, a professor of cell biology and physiology, and Arterburn, a regents professor of chemistry and biochemistry, have been working on uncovering this receptor with a team comprising members from both universities. The receptor could also be used to identify the presence of certain lung and endometrial cancers.

The two started studying the GPR30 receptor as a side project after Prossnitz learned about the receptor at a department presentation in 2002, he said. He said initial funding came from the Cowboys for Research Foundation and NMSU’s Tough Enough to Wear Pink campaign. He said some initial oddities especially piqued his interest.

“We got some strange, early results that were sort of bizarre,” Prossnitz said. “It had to do with where the receptor was mostly expressed in the cell and so forth.”

This inspired the researchers to continue with their research and start applying for grants, Prossnitz said. Grants have come from the National Institutes of Health and the National Cancer Institute.

They have also received financial support of about $200,000 from foundations connected to UNM, he said. Prossnitz estimates that overall, his team has received just under $5 million from various sources to fund the research.

Arterburn said the first thing doctors want to know when a woman is diagnosed with breast cancer is if it is estrogen receptor positive – that there are detectable levels of estrogen receptor protein in a tumor, which encourages the tumor to grow. And the duo hopes that a drug they are currently developing would counter the natural hormone estrogen and prevent growth, Arterburn said.

“We’ve been working on this other estrogen receptor, GPR30, that actually can deactivate it by some of the drugs that are meant to block the action of the nuclear receptor,” he said. “And so in combination with a program of screening small molecules, we have identified molecules that are selective for specific estrogen receptor types. We’re actively working on new leads as part of drug discovery efforts to try to develop more selective agents that will be able to control the action of estrogen in cancer.”

Prossnitz said women who need treatment for breast cancer take the drug Tamoxifen for up to five years to inhibit estrogen receptors.

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But the drug stimulates GPR30 and, consequently, cancer cells.

This can cause mutations and can make the cancer resistant to Tamoxifen, he said.

“In that case, the antagonist inhibitor that we’ve discovered could be used in some way on those resistant cancers,” Prossnitz said. “Either you could use right away in combination with Tamoxifen, or you could use it later when it’s resistant to Tamoxifen.”

But all of this information is still speculative, and they need to do further research in animal models, he said. They are currently into their first year of a five-year grant to study how the receptor GPR30 works in mice, Prossnitz said.

He said that if the experiments go well, his team can start looking for support from drug companies.

“We’re actively working on new leads as part of drug discovery efforts to try to develop more selective agents that will be able to control the action of estrogen in cancer,” Arterburn said.

However, to start doing human clinical trials and get their findings approved would cost a drug company around $1.3 billion, Arterburn said. He said very few molecules are able to advance to real drugs that are approved by the Food and Drug Association.

But Prossnitz remains hopeful that their research will be able to move forward.

“Our hope is that through the development, especially of these compounds, that they could be used either in the treatment of cancers, potentially preventatively or once the cancer is diagnosed,” he said.

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