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 c linical 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."