September 3, 2014

   A Publication of the James Buchanan Brady
   Urological Institute Johns Hopkins Medical Institutions

    Volume III, Winter 2007

THE PATRICK C. WALSH PROSTATE CANCER RESEARCH FUND AWARDEES

The Best New Drug May Be One That's Already Out There

It's an ambitious and ingenious idea, one that has great potential to help men with prostate cancer get new drugs much faster — and it could save millions of dollars, as well. There are an estimated 10,000 drugs already known to medicine and approved for use in patients. Many of them turn out to be helpful for more than one ailment. And yet, there's no centralized reservoir of knowledge about these drugs, says molecular scientist Jun Liu, Ph.D., the Peter Jay Sharp Foundation Scholar.

He is working to change this, and he's got many good reasons — at least 800 million of them. That's how many dollars it takes for just one new drug to be developed and brought, after many tests and clinical trials, to the patients who need it. Even with a host of scientific advances that have speeded up this process, "the average time from discovery to approval has more than doubled since 1964, from 6.5 to 14.8 years," Liu says. Even more sobering, he adds, less than one-quarter of the drugs that advance to Phase I clinical trials ever make it to the market. "Despite an almost thirty-fold increase to $33 billion in research and development from 1977 to 2003, the number of new drugs approved by the FDA remains relatively flat at 15 to 30 each year."

It takes, on average, nearly 15
years for a newly discovered drug
to make it to the people who need
it most. But there are thousands
of already-existing, alreadyapproved
drugs out there, waiting
to be tapped for new needs.

In contrast, the treasury of thousands of already-existing, already-approved drugs has been barely tapped. More than three years ago, Liu and his former graduate student, Curtis Chong, began an effort to systematically collect and screen all available FDAapproved drugs. So far, they have amassed a library that contains about 1,900 FDAapproved drugs and more than 600 that either entered Phase II clinical trials (were shown to be safe and to have few side effects) or were approved abroad for clinical use. From this research, "we have identified several drugs that possess potent and unexpected anti-angiogenic properties," Liu says. "Two of these, an immunosuppressive drug called mycophenolic acid, and an antifungal drug named itraconazole, have been shown to work in animal models of angiogenesis, or tumor growth."

With support from the Patrick C. Walsh Prostate Cancer Research Fund, he and colleagues continue to expand their library, and to examine the promising drugs they turn up. They are screening the library against prostate cancer cell lines, looking for novel drugs that inhibit the spread of cancer, or that seem to be more effective when combined with other drugs. "When we identify new inhibitors, we try to validate their mechanisms of action and see how well they work in different prostate tumor models in animals," Liu explains. "We are also carrying out follow-up studies on some of the most promising newly identified angiogenesis inhibitors, to facilitate their potential use in people with prostate cancer and other types of cancer."


 

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