The compound, tricirbine, was tested at various cancer centers from 1982 to 1996 and found to inhibit some cancers, but researchers failed to determine why. The Moffitt-USF team discovered that tricirbine works only against tumors in which the cancer-causing Akt protein is abundant and/or abnormally active.
"These tumors are addicted to hyperactive Akt and cannot survive without it," explains Saïd Sebti, Ph.D., Moffitt's Manuel and Adeline Garcia Professor, Leader of the Drug Discovery Program and Associate Director of Moffitt Research Institute. "What we discovered is a tailored therapy for tumors with a specific molecular signature."
Resurrecting tricirbine may be promising for patients with ovarian cancer, for instance, because "40 percent of women with ovarian cancer have tumors with high levels of active Akt," according to Sebti.
"To our knowledge, this is the first Akt inhibitor headed toward clinical trials," said Jin Cheng, MD, PhD, USF Professor of Pathology and Interdisciplinary Oncology.
Cheng and Sebti's study results were published in the journal Cancer Research.
VioQuest Pharmaceuticals Inc. (VQPH) of New Jersey is acquiring the licensing rights to the compound from USF through its merger with Greenwich Therapeutics Inc. and is planning clinical trials with Moffitt. The trials are expected to start within six to eight months. Patients will be selected for the trials based on whether their tumors have hyperactive Akt, which can be determined by a simple slide-stain test of tumor tissue.
Because tricirbine has previously been investigated in humans, the hypothesis-driven clinical trials planned at Moffitt can move directly into a PhaseI/II trial.
With the step-up of functional-genomics research at Moffitt and around the country, the advent of "customized medicine" has been heralded in headlines and at medical conferences. The clinical trial of this Akt-inhibitor is a concrete step toward that reality. Sebti says, "The beauty of this trial is that it's molecular therapy, based on the blueprint of the tumor cell."
About VioQuest Pharmaceuticals, Inc. VioQuest Pharmaceuticals is in the process of acquiring, developing and eventually bringing to market late pre-clinical and early clinical stage therapies for oncological, antiviral and autoimmune diseases. VioQuest's subsidiary Chiral Quest, a pioneer in asymmetric chemocatalysis chirality, offers unique synthesis processes based upon its proprietary technology. VioQuest provides its chiral products and services in all stages of product life cycles to well-known pharmaceutical and fine chemical companies worldwide. For more information, visit www.vioquestpharm.com.
In 2001, the National Cancer Institute awarded Moffitt the status of a Comprehensive Cancer Center in recognition of its excellence in research and contributions to clinical trials, prevention and cancer control. Additionally, Moffitt is a member of the National Comprehensive Cancer Network, a prestigious alliance of the country's leading cancer centers, and is listed in the U.S. News & World Report as one of the top cancer hospitals in America. Moffitt's sole mission is to contribute to the prevention and cure of cancer.
The University of South Florida Health Sciences Center is comprised of the colleges of Medicine, Nursing and Public Health and united by one mission "to advance collaborative learning and discovery leading to improved health in our community." USF has major affiliations with the area's teaching and research hospitals, providing an important diversity of educational experiences. In partnership with its affiliated hospitals, the Health Sciences Center's research funding jumped 21 percent last year to $145.4 million -- more than half of which came from federal sources.
Journal
Cancer Research