The Hepsin Discovery:

Potential for Hope in the Treatment of Prostate Cancer

Categories: Winter 2001

“The hope is that we’ve found a protein involved in the development and growth of prostate cancer.”

Prostate cancer specimens provided by Dr. William Catalona and financial support from the Urological Research Foundation have helped in the discovery of a protein, hepsin, that hopefully will lead to dramatic new methods for the treatment of prostate cancer.

“I think hepsin is important for prostate cancer growth,” Dr. Jeffrey Milbrandt said. “We just can’t prove it yet.”

Milbrandt was talking about the recent discovery that the protein hepsin is over expressed in a majority of prostate cancers.

Milbrandt’s findings, delivered at the latest CaP CURE prostate cancer conference, were confirmed by three other reports that listed hepsin as the number one candidate for further investigation.

“Hepsin has to be pursued,” Milbrandt said.

Dr. William Catalona, a co-author of the paper with Milbrandt, agreed. “The hope is that we’ve found a protein involved in the development and growth of prostate cancer,” Catalona said.

“If hepsin, is involved in the actual function of the prostate cancer cell, a drug could be targeted to inhibit this protein, a drug that would be effective in the treatment of prostate cancer,” Catalona said.

Contributing to Dr. Catalona and Dr. Milbrandt’s optimism for the hepsin discovery is the fact that the over expression of hepsin in prostate cancer cells occurs in a majority of patients with prostate cancer.

“If hepsin is involved in the development of prostate cancer and if a ‘target’ drug were to be developed to inhibit hepsin, it appears that this drug would have the potential to be effective for a majority of prostate cancer patients,” Milbrandt said.

“And since hepsin appears to be excessively produced in most prostate cancers, chemicals that block the actions of hepsin could possibly prevent prostate cancer from developing or progressing,” Catalona said.

“…a realistic hope for new and better ways to treate prostate cancer.”

Both Catalona and Milbrandt are hopeful about the discovery because hepsin has so many good features for drug development.

“Hepsin is up regulated a lot and therefore easy to knock out,” Catalona said.

In looking at overexpression in cells, 3-fold higher is usually worth noting. In hepsin, the over expression in cancer cells can be 10 to 100 times higher.

“Because it’s such a big difference, it’s more likely that by blocking the activity, we’ll be able to create a big effect,” Catalona said.

Hepsin has other good features for drug development. It’s located on the cell’s surface, which means it’s easier for drugs to get to it.

And, “It’s an enzyme in the family called serine proteases enzymes,” Milbrandt said. “We know quite a bit about them and we know that pharmaceutical chemists can create drugs to block this type of enzyme.”

Hepsin is also overexpressed in pin lesions (PIN) which are often a precursor to prostate cancer. If hepsin is found to play a major role in the development of prostate cancer, using it as an early diagnostic marker and then quickly inhibiting it would mean that patients could be treated in very early stages.

Identifying hepsin as a target is the first step but just because a protein is found up regulated in cancer cells doesn’t mean that the protein is a factor in the development of cancer.

“We have identified a very interesting target,” Milbrandt said, “But the information directing us to move forward will come in secondary experiments using mice models.

Milbrandt said that hepsin-deficient mice are available. They look fine and are overtly normal, which suggests that blocking hepsin in a living system doesn’t harm the system.

These mice models are being tested to find out if hepsin, or its absence, influences tumor growth.

“If we can show hepsin levels alter tumor growth, then drug companies will get involved,” Milbrandt said.

“Identifying hepsin as a target is the first step.”

Catalona wants prostate cancer patients to know that he believes hepsin has all the properties of a gene product that make it a potentially successful drug target.

“I want to point out to patients the realistic hope that with this new approach to drug discovery, there will be new and better ways of treating prostate cancer,” he said.

“I can’t give a time-line, but at the rate new discoveries are coming from genetics revolution and with our progress in putting together the missing pieces of the prostate cancer puzzle, things could happen quickly enough to benefit current patients.”

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