Researchers discover a potential target for therapy for patients with a deadly prostate cancer

November 8, 2010

A monoclonal antibody targeting a well known cell surface protein inhibited prostate cancer growth and metastasis in an aggressive form of the disease that did not respond to hormone therapy, according to a study by researchers with the UCLA Department of Urology and UCLA's Jonsson Comprehensive Cancer Center.

The researchers also found that the protein, N-cadherin, is up regulated or turned on in that does not respond to hormone therapy, known as castration resistant disease. The results of the study, done in cell lines and mouse models, were confirmed in humans after researchers examined tissue from dozens of men who died from prostate cancer, said Dr. Robert Reiter, a professor of urology, a Jonsson Cancer Center scientist and senior author of the study.

"This therapy may be particularly useful in men who are failing the newest forms of treatment that target the , which regulates testosterone," said Reiter, who is director of the cancer center's Specialized Program of Research Excellence (SPORE) in prostate cancer. "This could potentially offer an effective alternative or addition to those hormone therapies."

The study appears Nov. 7, 2010 in the early online edition of the peer-reviewed journal Nature Medicine.

The study represents a translational effort by Reiter and his team to take their basic science observations and transform them into new therapies for this aggressive form of prostate cancer to be tested in clinical trials. Observations made in those future clinical trials also could be used in the laboratory to refine potential therapies.

Reiter and his team first found that the N-cadherin gene was up regulated in castration resistant prostate cancer, presenting a potential target for therapy. The findings in cell lines and mouse models were confirmed by studying tissue from men who died from their castration resistant disease. Researchers then found that the up regulation is required to maintain castration resistant prostate cancers, meaning that the turning on of the pathway may be a cause of the hormone therapy resistance, making it an even more attractive target for therapy.

Armed with a hypothetical target at which to aim molecular therapies, Reiter and his team set out to develop novel therapeutics to block N-cadherin. They developed two 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. Reiter said this finding may mean the antibodies could potentially be used to block the spread of prostate cancer in men diagnosed with this aggressive form of the castration resistant disease, making it easier to treat and potentially improving outcomes in this patient population. It could also be effective in preventing men treated for early stage disease from progressing to castration resistance since the antibodies prevented that progression in the cell lines and mouse models, Reiter said.

"We believe these findings show that the up regulation 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," Reiter said. "These findings may provide us with yet another way to treat these cancers."

Although many men have indolent or slow growing prostate cancers that often are only observed over time, a significant percent of patients present with castration resistant disease or later develop castration resistance, which is very difficult to treat effectively. It would be very useful to have another tool in the arsenal to fight this type of prostate cancer, Reiter said.

The next step for Reiter and his team is to improve the antibodies and understand the mechanism by which N-cadherin works to promote resistance. Human clinical trials testing the antibodies would be opened in the future.

Reiter said his findings were somewhat surprising.

"We didn't think we'd see the level of activity that we did," he said. "And we didn't think the antibodies would block castration resistance."

Related Stories

Recommended for you

New findings explain how UV rays trigger skin cancer

October 18, 2017
Melanoma, a cancer of skin pigment cells called melanocytes, will strike an estimated 87,110 people in the U.S. in 2017, according to the Centers for Disease Control and Prevention. A fraction of those melanomas come from ...

Drug yields high response rates for lung cancer patients with harsh mutation

October 18, 2017
A targeted therapy resurrected by the Moon Shots Program at The University of Texas MD Anderson Cancer Center has produced unprecedented response rates among patients with metastatic non-small cell lung cancer that carries ...

Possible new immune therapy target in lung cancer

October 18, 2017
A study from Bern University Hospital in collaboration with the University of Bern shows that so-called perivascular-like cells from lung tumors behave abnormally. They not only inadequately support vascular structures, but ...

Many pelvic tumors in women may have common origin—fallopian tubes

October 17, 2017
Most—and possibly all—ovarian cancers start, not in ovaries, but instead in the fallopian tubes attached to them.

Researchers find novel mechanism of resistance to anti-cancer drugs

October 17, 2017
The targeted anti-cancer therapies cetuximab and panitumumab are mainstays of treatment for advanced colorectal cancer, the second leading cause of cancer-related deaths in the United States. However, many patients have tumors ...

New bowel cancer drug target discovered

October 17, 2017
Researchers at the Francis Crick Institute have discovered a new drug target for bowel cancer that is specific to tumour cells and therefore less toxic than conventional therapies.

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.