The potential for practical payoffs is significant, Bogyo said. Radiotherapy and many chemotherapeutic selectively damage DNA in rapidly replicating cells, dramatically boosting the amount of apoptotic death happening in tumors. Some experimental models indicate that inducing apoptosis is the main way these treatments kill cancer cells.
"Different individuals respond differently to a given treatment. The quicker you can make a decision about whether a drug is working or not, the better," Bogyo said. Moreover, he said, new-generation drugs, some of them now in clinical trials, are designed specifically to turn on caspases.
Because caspase activation is a very early event in apoptosis, monitoring it could speed clinicians' ability to determine whether, how and when these new drugs work, said Bogyo. He has started a company, Akrotome, to speed the fluorescent probes' development and commercialization. Stanford has licensed this technology to Akrotome for a 4 percent ownership stake.
"The entire cancer chemotherapy field is very, very excited about probes like this," said the Burnham Institute's Salvesen, who has no financial ties to the current study or to Akrotome. The approach also holds promise for tracking unwanted apoptotic damage to tissues in disorders such as macular degeneration or traumas such as post-ischemic reperfusion injury.
|Contact: Bruce Goldman|
Stanford University Medical Center