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Promising prostate cancer agent prevents AR signaling
A novel class of drug that disrupts androgen receptor signaling may some day provide a new therapeutic option for patients with advanced prostate cancer who fail androgen blockade.
A novel class of drug that disrupts androgen receptor signaling may some day provide a new therapeutic option for patients with advanced prostate cancer who fail androgen blockade.
A team of researchers from the University of Texas Southwestern Medical Center, Dallas found that they could disrupt androgen receptor signaling using a class of drugs called peptidomimetics. This therapeutic agent consists of an engineered small protein-like chain designed to mimic peptides. The peptidomimetic agents block the activity of the androgen receptor even in the presence of androgen by attacking the protein in a different spot from where the androgen binds.
“We are hopeful that this novel class of drugs will shut down androgen receptor signaling and lead to added options and increased longevity for men with advanced prostate cancer,” said senior author Ganesh Raj, MD, PhD.
Instead of targeting the androgen receptor (lock) or androgen production (key) in advanced prostate cancer, peptidomimetics uncouple the lock and key mechanism from the proliferation signal. Thus, even with the androgen receptor activated, the prostate cancer cells do not receive the signal to proliferate and do not grow.
The authors tested their investigational drug in mouse and human tissue models. The drug proved non-toxic and prevented androgen receptor signaling in cancer cells, they reported. The response is highly promising, the researchers said, and suggests that peptidomimetic targeting of prostate cancer may be a viable therapeutic approach for men with advanced disease.
Further testing is needed before a drug could move to phase I clinical trials.
“Most drugs now available to treat advanced prostate cancer improve survival rates by 3 or 4 months,” Dr. Raj said. “Our new agents may offer hope for men who fail with the current drugs.”
These findings represent the development of a first-in-class agent targeting critical interactions between proteins. Other cellular and disease processes eventually could also be targeted with peptidomimetics, the scientists said.
The Prostate Cancer Foundation, the Dorothy and James Cleo Thompson Foundation, and the Robert A. Welch Foundation funded the research.
Study results were published online in Nature Communications (May 28, 2013).
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