Researchers at University of Cincinnati taking the lead on ovarian, head and neck cancer studies

CINCINNATI -- The University of Cincinnati is breaking ground with studies focusing on two types of highly fatal, chemoresistant cancers.

Researchers will examine factors present in ovarian cancer as well as head and neck cancer, looking at how the body's own immune system promotes or inhibits growth. The university received nearly $70,000 in grants to fund the studies.

As a principal investigator in an ovarian cancer study at the University of Cincinnati, Dr. Chunying Du is looking into the connection between the BRUCE protein and cancer resistance. Photo provided

With National Ovarian Cancer Awareness Month observed in September, principal investigator Dr. Chunying Du said it's especially important to recognize the impact on women, as there are more than 22,000 new cases diagnosed and 14,000 deaths each year.

As part of the ovarian cancer study, she said they'll be looking at the high levels of a single protein known as BRUCE (BIR repeat containing ubiquitin-conjugating enzyme) that's found in reoccurring cases.

"So this study will lay the foundation for the future to really find a way to lower the level of BRUCE in hope to make cancer cells more sensitive to chemotherapy," she said.

The BRUCE protein has two major functions in the cell: It keeps cells from dying and effects DNA repair within the cells, she said. Sometimes BRUCE goes awry after completion of chemotherapy treatment and begins defending and repairing cancer cells, rendering them chemoresistant. She said that in all cases studied so far, women with reoccurring ovarian cancer have all shown high levels of BRUCE.

"Chemotherapeutic drugs kill cancer cells, but BRUCE itself prevents cell death and if they have high levels of BRUCE, the ovarian cancer cells have probably have acquired higher capabilities to resist cell death," Du said.

In addition to testing for the BRCA1 and BRCA2 genetic mutations linked to ovarian and breast cancer, she said testing for high levels of BRUCE may be used in the future as a genetic marker for potentially contracting those diseases.

Researchers will collaborate with the UC Medical Center to study cancer cells from current patients as well as cell lines from the lab. During the yearlong study, Du said she hopes to show by increasing and decreasing levels of BRUCE, a change in responsiveness to chemotherapeutic drugs will occur.

In addition, she said BRUCE can also be tied to a number of other reoccurring cancers.

"There are ways to effectively lower the level of BRUCE protein that can actually be done," Du said. "So there is a very important need for our basic research scientists to collaborate with clinicians and physicians to combine our knowledge to find an effective fight for this chemoresistance."

The head and neck cancer study will examine the impact of dopamine in both the development and reduction of secondary tumors. Researchers will look at repurposing drugs currently approved by the U.S. Food and Drug Administration for treatment. This study comes on the heels of another by the team also linking dopamine with breast cancer.

According to principal investigator Nira Ben-Jonathan, who also holds a doctorate in philosophy, neurologists usually associate dopamine with diseases like Parkinson's disease, schizophrenia or certain addictive behaviors. As dopamine is a neurotransmitter that sends messages to nerve cells, she said, no other research prior to theirs has connected it to cancer.

"When I wrote the paper and the grant proposal, they said, 'Why hasn't anyone shown this before?' and I said, 'This is how inventions come to be: You discover something new,'" Ben-Jonathan said.

Ben-Jonathan first became interested in dopamine while studying its effects on hormones produced by the pituitary glands. She said their research eventually led them to discover that when a certain type of dopamine called D1R was activated, it killed breast cancer cells in mice. However, only metastasized tumors and not the primary tumor was affected, she noted.

"We need to do a much larger study and show that metastasis responds and if metastasis responds, then advanced cancer will be the one we target, not the primary cancer," Ben-Jonathan said. "The primary cancer is not nice to have, but that's not what's killing you. It's when it spreads to the brain, liver, lungs and bones."

During their breast cancer study, she said they focused on drugs already approved by the FDA for treatment, like Fenoldopam, which is normally used to treat hypertension. She said the upside of repurposing a drug is that it takes a far shorter time to be approved, as it has already passed the stringent process that normally takes 10 to 15 years.

In terms of the head and neck cancer, Ben-Jonathan said, they're currently testing erectile dysfunction drugs such as Cialis, which affects dopamine D1R, ultimately killing cancer cells.

"We found several drugs -- some of them are already approved by the FDA -- to treat other things that really can suppress tumor growth in anyone," she said. "That is the take-home message."

Ben-Jonathan hopes findings from both the breast cancer study and current head and neck cancer study will grab the attention of other clinicians and drug companies. The more interest they generate, she said, the more expeditiously clinical trials will move forward in humans.

"(Chinese philosopher) Lao Tzu said, 'The journey of a thousand miles begins with one step.' We are in a few steps of the thousand miles," Ben-Jonathan said. "Sometimes you feel a bit weak in the legs because you think, 'What if I am wrong?' But you check yourself and you test it and then you say, 'I'm a good scientist, I know what I'm doing. I really think that I've found something here.'"

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