Two Washington State University researchers who developed a compound that may help treat patients with early-stage Alzheimers disease now are testing a compound they believe might immobilize cancer tumors and kill cancer cells.


Psychologist Jay Wright says he and Joe Harding, a biochemist with WSUs veterinary school, have been developing in Pullman a compound they call Dival, which they claim halts the growth of cancer tumors. The researchers, who have been testing Dival on mice with breast cancer since 1998, hope the drug will be manufactured for human use within the next five to six years.


This is all based on mouse and rat stuff now, so it could all be pie in the sky, Wright says. But things are looking pretty good so far.


He says he and Harding have spent about $850,000 researching the receptor that Dival blocks. Theyre doing the research through a company they founded called Pacific Northwest Biotechnology Inc. (PNB), and with the assistance of a small group of WSU students. Though they havent published any articles about their breast-cancer tests yet, one pharmaceutical company has approached them about the potential drug, he says.


After more testing, they may seek an agreement with a biotech or drug company and sell the compound, which they hope the U.S. Food and Drug Administration will allow through clinical trials quickly, he says.


It has become a real-world issue for us, he says. I dont want to be on my deathbed and wonder if we could have discovered something really important.


Current FDA-approved treatments for tumor-related cancers typically involve surgical removal of the growth and subsequent chemotherapy or radiation treatments, which help prevent cancer-cell duplication, Wright says. Chemotherapy and radiation can be effective especially if the tumor is removed before it metastasizesor spreadsbut they can cause severe side effects such as gastrointestinal problems and nausea, he says.


PNBs research shows that treatment with Dival arrests tumor growth by stopping new blood-vessel formation, which it accomplishes by blocking whats called the angiotensin receptor protein subtype four, Wright says. That receptor is vital for new blood-vessel growth, so stopping it cuts off blood flow to a tumor, so it cant grow, he says.


Tumor-related cancers such as breast and prostate cancer account for 80 percent of all cancers, Wright says. According to the American Cancer Society, breast cancer is the second most common cancer in women, and at 211,000 new cases per year, it represents nearly a third of all cancers for women. Prostate cancer accounts for a third of all cancers for men.


Since Dival primarily interferes with tumor growth, it wouldnt be used for treating leukemia, but may be effective in treating colon and other high-incidence cancers, he says.


Wright says he and Harding also have found that Dival may kill cancer cells, much like chemotherapy and radiation does. More research must be done, however, to support those findings, he says.


Howard Hosick, another WSU genetics and cell biology professor, told Wright and Harding that if Dival works, it likely would be administered to cancer patients as soon as the diagnosis is made, Wright says. Doctors then would treat patients with Dival before surgery to stop tumor growth, and after surgery, perhaps in combination with chemotherapy and radiation, he says.


I wouldnt say Dival would take away chemotherapy, he says. But it might enable patients to cut back on chemotherapy so its not as devastating.


Also, Dival treatments likely would be less expensive than chemotherapy and radiation, Wright says. Treatment with the pellets, which would be inserted under the skin and would release the drug inside the body over four to six weeks, would cost about $25 per treatment, he says.


Genentech, of San Francisco, recently received FDA approval for a drug called Avastin, which also stops the formation of new blood vessels, but by interacting with a different receptor than what Dival blocks, Wright says. Avastin is estimated to cost $250 per treatment, he says.


Wright says he hopes Dival will be ready for toxicological trials within about a year.


Initial discovery


Wright says that when he and Harding began working together in the late 1970s, they focused their research on treatments for high blood pressure. While looking for a receptor relating to hypertension, Harding discovered the angiotensin receptor protein subtype four.


The pair began researching memory-facilitating compounds that activate the receptor and developed a drug they call Norleu, which enhances a neurotransmitter that Alzheimers patients lack, Wright says. They expanded their research beyond the central nervous system after a few students discovered that the receptors were located in structures such as the heart, liver, and intestines.


Wright and Harding found that when they blocked the receptors, new blood-vessel formation stopped. They took their findings to Hosick, who suggested they test their research on mice with implanted breast-cancer cells, Wright says.


The researchers injected slow-release drug pellets into the mice and soon found that the drug slowed the growth rate of tumors by 90 percent or more in some mice groups, he says.


The researchers also tested the drug after allowing the tumors to form for about eight weeks after implanting breast-cancer cells in the mice, about the maximum amount of time allowed under guidelines for the humane treatment of animals, Wright says. They discovered that even with giving the tumors a head start, the drug still stunted their growth and possibly killed cancer cells, he says.


If the drug can stop cancer-cell duplication, people may only need to take it for a few months, and not for the rest of their lives, he says.


Because Dival appears to stop all new blood-vessel formation, children and pregnant women wouldnt be able to use it, Wright says. So far, it doesnt seem to harm existing blood vessels, he says.


Other possible side effects, such as hair loss and decreased sense of taste, are no worse than the negative effects of chemotherapy, Wright says.


If we have something that causes less of an impact and can be just as effective, it may give physicians and patients down the road another choice or another combination of choices, Wright says.


The price of research


Wright says that he and Harding will need about $100,000 to refine administration methods of the drug before it can go through toxicological testing. He says they may seek another grant from the National Institute of Health, which gave them about $140,000 for their initial breast-cancer research.


If they secure more funding, the researchers will explore other ways of delivering the drug besides the pellets, Wright says. They are looking into innovative methods being developed to treat diabetic patients, including inserting drugs into plastic wafers that are implanted under the skin, he says.


After that research, PNB will need to raise another $500,000 to $750,000 to pay for the drugs toxicological testing, which would take from six months to a year, Wright says. Though they havent seen any major side effects, any toxic findings during those tests could set back the drugs move toward FDA approval, he says.


We dont have any illusions about it not being a steep climb, he says.


The researchers may decide to sell the drug to a pharmaceutical company after the toxicological trials or the first phase of clinical trials, he says.


Wright and Harding now are developing another compound to treat prostate cancer.


Wright says funding presents a challenge, but says that he and Harding will continue to seek investors who will help them develop their research into useable drugs.


Theyll continue conducting their research in a laboratory at WSU, which holds the patent on the angiotensin receptor they discovered, Wright says. PNB has a patent pending on Dival.


Wright says it may surprise some people to find out about their research.


How many people specifically come down to Pullman and say, What kind of drugs do you have here? he says. Its good for people to realize there are research programs going on in their backyards.