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Florida Institute Close to Testing New Cancer Treatment

Posted on: Thursday, 23 June 2005, 15:00 CDT

Jun. 23--TAMPA -- Almost a decade ago, a promising cancer-fighting compound was abandoned because it was unpredictable and risky.

Now, triciribine has become a hot property for H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida. Its Drug Discovery team uses molecular therapy to turn the chemical into a heat-seeking missile against tumors.

A drug company is paying USF an undisclosed amount for licensing rights and expects to co-sponsor clinical trials for Moffitt patients this year.

"The science is very exciting," said Daniel Greenleaf, president of VioQuest Pharmaceuticals Inc. of New Jersey. "This particular therapeutic is right on the cutting edge."

It's a long shot, perhaps, but if the treatment lives up to its early promise, it could prove useful in many types of cancer, USF researchers and the company say.

Although the licensing deal doesn't bring biotechnology jobs to Tampa Bay, news of it puts Moffitt/USF's Drug Discovery program on the map, USF officials say. Only a few other U.S. universities, including Stanford and Harvard, have the capability of bringing a cancer compound from the laboratory to human trials in one site.

The trip from test tube to clinical trials will have taken only three years -- a remarkably rapid pace made possible by mining previously tested compounds. It shows the wisdom of teaming USF laboratory scientists with Moffitt's clinical researchers, said Stephen Klasko, vice president of USF Health Sciences Center and dean of USF College of Medicine.

"It's the beginning of everything we hoped the collaboration would accomplish," he said. "This portends our ability to build a true center for drug discovery."

VioQuest presented news about the compound, now called API-2, at this week's international biotechnology conference in Philadelphia.

Greenleaf said investors, drug companies and researchers all showed avid interest.

Co-discoverers of API-2 at USF are Jin Cheng, USF professor of pathology, and Said Sebti, associate director of Moffitt Research Institute and its program leader for drug discovery. Their study, published in the journal Cancer Research in July, reported that low doses of triciribine were effective in stopping growth of certain human tumors that had been grafted onto mice. They reported no side effects.

Their hypothesis is that the compound kills tumors that have overactive Akt proteins, which are implicated in cancer. Hyperactive Akt proteins resist standard cancer drugs. When Cheng and Sebti expose tissues carrying the proteins to the compound, they say, it calms them down and the tumors stop growing.

USF patented the use of triciribine in hyperactive Akt, calling the resulting drug API-2. A known compound can be patented if a new use for it is found.

A major attraction of API-2 to drug companies is that hyperactive Akt is so common -- found in more than half of tumors, Cheng said.

It's found in an estimated 40 percent of patients with breast cancer, 30 percent with colon cancer and 50 percent with melanoma.

"We're going after a magic bullet here," Sebti said.

His optimism lies in a new understanding of the molecular structure and genetic quirks of tumors. Not so long ago, cancers were classified by the organ in which they originated: stomach, brain, uterus, etc. That was convenient but wasn't helpful for treating them because there are different types of cancers that originate in each organ, including at least five types of breast cancer.

Researchers in the 1980s and '90s found that triciribine worked on some tumors but not others, and they couldn't see the pattern. To make things worse, they were using a high dose that gave a lot of patients symptoms of diabetes. So in the mid-1990s, cancer researchers gave up on it.

Nothing more happened until Sebti received 2,000 compounds from the National Cancer Institute's database of chemical compounds. He asked Cheng, who had worked extensively on Akt, to test the most promising ones on it.

After Cheng and Sebti reported that API-2 showed promising results in mice last year, USF's patent and licensing office began to get calls. Greenwich Therapeutics, a small privately held New York biotechnology company, grabbed the licensing rights. It had clinical trials on another antitumor drug ongoing at the Cleveland Clinic.

VioQuest, a publicly traded company that develops promising therapies for cancer and other diseases, announced last month that it was merging with Greenwich.

If the Food and Drug Administration approves the application for clinical trials of API-2, as expected, they will begin in about six months. Moffitt doctors will try it only in cancers that have resisted standard therapy and only in a few dozen patients at the outset. Although it's too soon to predict which classes of cancer will be included, hyperactive Akt is found in a number of types of cancer, including breast, colon, ovarian, pancreas and melanoma.

Patients who want to participate will have their tumor tissue tested to see whether they have hyperactive Akt. If so, they'll be given the drug intravenously and undergo another biopsy a week later to see whether it's working. These steps are designed to prevent patients who have no hope of benefiting from getting the drug.

Sebti said susceptible tumors respond to a very low dose of API-2, a level found safe in the past. So he expects no serious side effects.

USF/Moffitt and VioQuest plan to combine the first and second phases of the usual three-stage clinical trial process. If all goes well, API-2 could win FDA approval in two to three years.

Of course, it's also possible that humans won't respond as well as mice. There may be interference from some other genetic mischief-maker in addition to the Akt.

"Cancer is very complicated," Sebti said. "I've been in this business almost 30 years, and I'd be naive to say it will work in all patients with Akt."

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Source: Tampa Tribune

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