The biomarker, prostate specific membrane antigen (PSMA), which is abundantly present in cells of patients with advanced prostate cancer, has a contributory role in the progression of cancer to an aggressive disease according to work published in the July issue of Molecular Cancer Therapeutics, an American Association for Cancer Research journal, and provides new insights into therapeutic benefit for patients with advanced prostate cancer.

The research was conducted by Dr. Ayyappan K. Rajasekaran, the Director of the Nemours Center for Childhood Cancer Research (NCCCR), and his research team while they were at the University of California, Los Angeles, and at NCCCR. The abundance of PSMA in prostate cancer cells increases as the cancer progresses into a metastatic and hormone-independent advanced disease. Dr. Rajasekaran said, "We strongly suspected that PSMA has a potential role in the progression of prostate cancer into an aggressive disease. But how it participates in disease progression was not clear. Now in this study, we identified that PSMA does have an important causative role in prostate cancer progression."

This study was initiated when the researchers found that PSMA was present at the poles of the dividing cells. These poles are complex structures at the opposite ends of the cells that control the separation of chromosomes equally into daughter cells during cell division. "Presence of PSMA at the poles indicated it might have a role in cell division and chromosome segregation, and we continued our quest to understand this potential function of PSMA," said Dr. Rajasekaran.

Rajasekaran and his research team found that PSMA-expressing cells spent less time dividing. They found that PSMA interferes with the function of the regulatory protein anaphase-promoting complex (APC) and induces aneuploidy in cancer cells. "When PSMA is present, cells hurried to complete their division prior to having all their chromosomes properly segregated," said Dr. Rajasekaran.

PSMA is present in prostate cancer cells but not in normal cells. Therefore, it is an excellent therapeutic target for prostate cancer. There are several ongoing clinical trials for PSMA-based therapeutic interventions. "Since PSMA expression is higher in metastatic compared to benign cancer cells, anti-PSMA-based therapeutic strategies should target metastatic prostate cancer cells, which will benefit patients with advanced prostate cancer," the study states.

Dr. Rajasekaran and his team conducted their research on cell lines and are in the process of translating their findings into human clinical trials, which should be available in two to three years.