Daniel Frigo and his team are working to develop the next generation of prostate cancer therapies targeted at metabolism. | Courtesy of Jessie Villarreal
Although prostate cancer is a fairly treatable disease in its early stages, it can begin to spread throughout the body if left untreated.
Daniel Frigo, professor and scientist with the UH Center for Nuclear Receptors and Cell Signaling, and his team are working on ways to target prostate cancer at the cellular level, specifically focusing on the androgen receptor overriding a metabolic pathway that drives the cancer itself.
In a normal cell, metabolic pathways are a series of chemical reactions catalyzed by enzymes that allow for cell growth and maintenance. A cell takes in a certain amount of sugars and nutrients to make the fundamental building blocks in the body. The androgen receptor essentially hijacks normal processes that a cell uses to respond to changes when using various nutrients. From this hijacking, the androgen allows a hyper-proliferation of the cell, and in turn, the cell starts taking in sugars and materials from the outside at a much faster rate than it normally does, making more cancer cells.
Androgen suppression is the normal therapeutic treatment to prostate cancer in its early stages. As the cancer progresses into a stage known as castration-resistant, androgen suppression is no longer effective.
“These types of treatment, they work for a couple of years, but they always fail after about two or three years,” Frigo said.
Frigo’s goal is to target the affected metabolic pathway and find what gene is actually driving the cancer itself.
“If we can figure out what’s downstream, then we’re going to start to identify new therapeutic targets with the hope that if we do this, then you can find new things you can possibly drug or manipulate through different approaches,” he said. “You can develop therapies that are going to theoretically have fewer side effects. That’s sort of how we got into our research — we’re hunting down new pathways that are regulated by an androgen receptor.”
About a quarter of all U.S. cancer cases are prostate cancer, Frigo said. Prostate cancer isn’t deadly most of the time, but there are still enough malignant cases per year that prostate cancer is one of the deadliest diagnosed cancers in the U.S.
“Just because you get diagnosed with it, doesn’t mean it’s a death sentence,” Frigo said. “More times than not, you can treat it.”
Frigo and his team have discovered two proteins they can work with that will potentially lead to more knowledge about how the androgen receptor is triggering the cancerous pathway.
“We’ve put an emphasis on trying to identify pathways we think we can actually do something about,” Frigo said.
By using the kinase protein known as CaMPKK2 that is targeted by another protein, AMPK, it allows for a more selective expression, and it is unique to the prostate in that it is druggable and therefore could become a therapeutic treatment. If AMPK isn’t the best of targets, there could be proteins downstream or upstream that can serve as better targets, and this is what Frigo is looking toward.
The important part of the research is identifying at what stage of the disease process the pathway is being affected, Frigo said. The next step in this research is to get to patient trials.
“The phase that we’re taking to now is pre-clinical, because you have to go test it out in this route and make sure that it’s a bona fide therapeutic target,” Frigo said.
To fund this project, Frigo has pulled in grants from numerous groups such as the National Institute of Health, the Department of Defense and Golfers Against Cancer — a small group of golfers that has grown to raise funds at a national level.
“Those types of organizations are the best, because they give you the money that gives you a little bit of liquidity, so you can actually say if you see something exciting, you can put a lot of resources in it very quickly,” Frigo said.
The idea for this project originated at Duke University, where Frigo completed his fellowship. Frigo came to UH in 2010, and his project has continued since 2011, when his laboratory opened.
“I’ll take it as far as it goes,” he said.
