Testing Prostate Cancer Therapies Using a Co-Clinical Trial
Bonnie Prescott BIDMC staff
NOVEMBER 01, 2015
“When a patient’s diagnosis is latter-stage prostate cancer, the standard treatment is androgen deprivation therapy [ADT],” says Bubley, Director of the Genitourinary Cancer Program in the Cancer Center at Beth Israel Deaconess Medical Center. “ADT works by lowering testosterone production and thereby depriving prostate tumors of the ‘fuel’ that helps them grow.”
But, he adds, although this hormone therapy is almost always effective, all tumors eventually grow resistant to ADT — and cancer recurs. Over the past two years, Bubley has been part of a BIDMC scientific team that has been testing a targeted treatment alternative for late-stage prostate cancer using a unique type of study known as a “ Co-Clinical Trial.”
This new approach to clinical research — in which specially-created mouse models with genetic mutations are matched with tumor tissue from human cancer patients in order to test new therapies — was developed by BIDMC Cancer Center Director Pier Paolo Pandolfi, MD, PhD.
“Targeted therapies are designed to attack cancers by pinpointing the genes and genetic mutations that underlie diseases,” says Pandolfi (right). “The problem is that cancer cells are genetically complex, sometimes containing hundreds of genetic mutations. We needed to develop a way to cut down on all this ‘genetic noise’ to get at the root of the disease. The Co-Clinical Trial enables us to streamline and expedite the process in order to more quickly test a variety of new cancer drugs.”
Here’s how it works: In the Co-Clinical Trial, human participants are matched with animal models that have been genetically engineered to carry different combinations of just a few major human prostate cancer genes.
“When the animals develop tumors — just as the human patients did — they will receive the same therapies as the patients receive,” says Bubley (right). But, he adds, because each animal has only a few mutations, the researchers will be able to quickly assess which treatments are effective and which are not — and will be able to go back and adjust treatment accordingly for the human patients.
A particular advantage to this approach, say Bubley and Pandolfi, will be the ability to test combinations of different drugs to treat prostate cancer and overcome ADT resistance.
“Going forward, we think that combinations of targeted and conventional therapies may prove to be effective, particularly for drug-resistant disease,” says Bubley. “And the only realistic way to be able to quickly test numerous different drug combinations will be through the Co-Clinical Trial process.”