Targeting metabolism to develop new prostate cancer treatments

February 28, 2014
Targeting metabolism to develop new prostate cancer treatments
Daniel Frigo is looking at a cascade of biochemical reactions inside the cell, focusing on an enzyme considered a master regulator of metabolism. Frigo hopes this research will unlock more effective and less harmful prostate cancer treatments. Credit: Jessie Villarreal

A University of Houston (UH) scientist and his team are working to develop the next generation of prostate cancer therapies, which are targeted at metabolism.

With approximately one out of six American men being diagnosed and nearly a quarter of a million new cases expected this year, is the most common malignancy among men in the U.S. Since prostate cancer relies on androgens for growth and survival, androgen ablation therapies are the standard of care for late-stage disease. While patients initially respond favorably to this course of treatment, most experience a relapse within two years, at which time limited treatment options exist. At this stage, known as castration-resistant prostate cancer, androgen-deprivation therapies are no longer effective, but interestingly, androgen receptor signaling is still active and plays a large role in the progression of the cancer. Because of this, both and the processes downstream of the receptor remain viable targets for therapeutic intervention. Unfortunately, it is unclear which specific downstream processes actually drive the disease and, therefore, what should be targeted.

Daniel Frigo, an assistant professor with the UH Center for Nuclear Receptors and Cell Signaling (CNRCS), has set his sights on a particular cascade of biochemical reactions inside the cell. Focusing specifically on an enzyme known as AMPK, which is considered a master regulator of metabolism, Frigo and his team have demonstrated that androgens have the capacity to take control of this enzyme's molecular signals.

"The androgen signaling cascade is important for understanding early and late-stage prostate cancer progression," Frigo said. "We found that when androgens activated this signaling pathway, it hijacked normal conditions, allowing the tumor to use diverse nutrients to the detriment of the patient. These results emphasize the potential utility of developing metabolic-targeted therapies directed toward this signaling cascade for the treatment of prostate cancer, and we look forward to exploring this and other further in order to develop the next generation of cancer therapies."

In their studies, Frigo's team showed that prostate cancer cells respond to androgens not only by increasing the breakdown of sugars, a process known as glycolysis that is commonly seen in many cancers, but also escalating the metabolism of fats. While much of the research on cancer metabolism has historically focused on glycolysis, the researchers say it's now becoming apparent that not all cancers depend solely on sugars.

Their findings further indicate that the metabolic changes brought about by the AMPK enzyme result in distinct growth advantages to . They say, however, that our understanding of how androgen receptor signaling impacts cellular metabolism and what role this has in disease progression remains incomplete.

The Frigo lab is one of several within the CNRCS concentrated on the role of in cancer prevention and treatment, and his team has long studied the androgen receptor, which turns on or off various signaling pathways. Frigo believes these pathways hold the potential for better cancer treatments. Targeting these underexplored metabolic pathways for the development of novel therapeutics, Frigo's ultimate goal is to unlock more effective and less harmful cancer treatment alternatives.

With funding from the Department of Defense, National Institutes of Health, Texas Emerging Technology Fund and Golfers Against Cancer, Frigo's latest research appears in Nature's Oncogene. One of the world's leading cancer journals, Oncogene covers all aspects of the structure and function of genes that have the potential to cause cancer and are often mutated or expressed at high levels in tumor cells.

Explore further: Classic signaling pathway holds the key to prostate cancer progression

Related Stories

Classic signaling pathway holds the key to prostate cancer progression

December 20, 2013
University of Houston researchers published a study investigating the processes through which androgen receptors affect prostate cancer progression. The publication, "Androgens Regulate Prostate Cancer Cell Growth via an ...

Study identifies a key cellular pathway in prostate cancer

February 10, 2014
Mayo Clinic researchers have shed light on a new mechanism by which prostate cancer develops in men. Central to development of nearly all prostate cancer cases are malfunctions in the androgen receptor—the cellular component ...

Noninvasive assay monitored treatment response in patients with metastatic prostate cancer

October 23, 2012
Deciding the ideal treatment for patients with metastatic prostate cancer that stops responding to initial therapy could be guided by certain analyses of cancer cells isolated from the patients' blood, according to data published ...

Researchers identify novel class of drugs for prostate cancers

May 28, 2013
A new study on prostate cancer describes a novel class of drugs developed by UT Southwestern Medical Center researchers that interrupts critical signaling needed for prostate cancer cells to grow.

Study finds genetic mutation in castration-resistant prostate cancer

August 29, 2013
The mutation occurs in the androgen-synthesizing enzyme 3βHSD1 in castration-resistant prostate cancer (CRPC), according to research published online today in Cell. This mutation enables the tumor to make its own supply ...

New medication treats drug-resistant prostate cancer in the laboratory

June 17, 2013
A new drug called pyrvinium pamoate inhibits aggressive forms of prostate cancer that are resistant to standard drugs, according to a study conducted in an animal model. The results will be presented Monday at The Endocrine ...

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.