Antibody inhibits growth of castration-resistant PCa

A monoclonal antibody targeting a well-known cell-surface protein inhibits the growth and spread of castration-resistant prostate cancer, say researchers from UCLA.

The researchers also found that the protein, N-cadherin, is upregulated in castration-resistant disease.

The results of the study, conducted in cell lines and mouse models, were confirmed in humans after researchers examined tissue from dozens of men who died from the disease, said senior author Robert Reiter, MD, of UCLA’s Jonsson Comprehensive Cancer Center.

"This therapy may be particularly useful in men who are failing the newest forms of treatment that target the androgen receptor," Dr. Reiter said. "This could potentially offer an effective alternative or addition to those hormone therapies."

Armed with a hypothetical target at which to aim molecular therapies, Dr. Reiter and his team set out to develop novel therapeutics to block N-cadherin. They developed two monoclonal antibodies to test on their cell lines and animal models and found that the antibodies slowed the growth in their prostate cancer cell lines and mouse models and blocked the spread of castration-resistant prostate cancer in mouse models.

Dr. Reiter said this finding may mean the antibodies could potentially be used to block the spread of prostate cancer in men diagnosed with castration-resistant disease, making it easier to treat and potentially improving outcomes in this patient population.

"We believe these findings show that the upregulation of N-cadherin is one of the mechanisms that leads to castration resistance, and it could be targeted, perhaps in conjunction with other pathways already being studied that lead to resistance," Dr. Reiter said. "These findings may provide us with yet another way to treat these cancers."

Study results were published online in Nature Medicine (Nov. 7, 2010).