The National Institutes of Health has awarded a USC Norris Comprehensive Cancer Center research team a three-year, $1.6 million grant for a clinical trial of a new drug to treat advanced prostate cancer. The drug holds promise for targeting only the diseased cells and avoiding side effects.
As the primary investigator, Jacek Pinski, associate professor of medicine at the Keck School of Medicine of USC, will conduct a trial of the new anti-cancer drug, AEZS-108 (AN-152). Pinski will lead a team that uses new methods for collecting and analyzing data about the drug’s effectiveness.
AEZS-108 couples a peptide, LH-RH, with the chemotherapeutic agent doxorubicin to directly target cells that express LH-RH receptors – specifically, prostate cancer cells, Pinski said.
“Because the drug is expected to be delivered specifically to the cancer cells, we hope to avoid damaging healthy tissue and side effects,” he said.
Prostate cancer is primarily a disease of older men, who often have other medical conditions, so the toxicity of medication is a great concern during cancer treatments.
Because prostate cancer grows when exposed to testosterone and related hormones, the primary treatment for patients with advanced prostate cancer is therapy to stop the production of these hormones. This treatment is usually effective for about 24 months, and then typically the cancer evolves to a state of “castration resistance.”
For men with castration-resistant prostate cancer, the chemotherapeutic agent docetaxel has been shown in two large clinical trials to prolong survival. Those who do not respond to docetaxel therapy, whose response falters or who cannot tolerate the drug are left with limited options.
Several studies have shown a generally poor response to second-line chemotherapy in castration-resistant prostate cancer, prompting a search for more effective options.
In previous research, Pinski found that cancerous cells in human prostate tissue contain a unique protein on their surface called luteinizing hormone-releasing hormone receptor (LH-RH).
Andrew Schall, a Nobel Prize laureate who will collaborate on Pinski’s upcoming study, developed AN-152, a compound that specifically damages cells containing this protein, including prostate cancer cells.
The commercial name of AN-152 is AEZS-108, produced by Aeterna Zentaris Inc. The drug has been studied in gynecologic cancers in women and has been shown to be effective and well-tolerated. Preclinical studies of animal models with prostate cancer also have demonstrated positive results with the drug.
The research also will break new ground with its related studies.
In one, researchers will examine the correlation between the expression of LH-RH receptors on circulating tumor cells in the blood and the clinical outcomes of patients taking the new drug – how long until they respond to treatment, whether the drug prolongs survival and the degree of toxicity.
Another study will take advantage of the autofluorescent characteristic of AEZS-108 to see if the drug enters into the circulating tumor cells of patients’ blood samples.
To conduct these studies, tumor cells will be collected with a new, porous artificial-membrane device, developed in cooperation with Yu-Chong Tai of the California Institute of Technology. The device may be speedier and less expensive to use than existing methods.
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