“Most cancers have elevated levels of procaspase-3,” Hergenrother said. “When it is turned on, procaspase-3 kills cells.”
“PAC-1 restores the activation of procaspase-3 and, because this enzyme is elevated in cancer cells, targets cancer cells over noncancerous cells,” he said.
“This requires that the rodents be immunocompromised to mitigate rejection of human cells,” he said. “As such, most rodent tumor models do not faithfully recapitulate the tumor microenvironment – in particular, the body’s immune surveillance of the tumor.
“I look at pets with spontaneous tumors as being complementary to rodent models and recognize that not all discoveries in pet dogs will necessarily translate similarly to people,” Fan said.
“Glioblastoma multiforme has this feature of spreading silently along the blood vessels inside the brain,” he said. “That’s a reason why most patients will unfortunately have disease coming back later on after surgery and radiation.”
“All three dogs had, at the very least, what we call a partial response, which means more than a 30 percent reduction in the tumor,” he said. “And one of the dogs had a complete response, as identified with serial MRI scans, with a 100 percent reduction in the tumor mass 84 days after combination therapy.”