Using translational research to help cancer patients

When he arrived at Columbia from Duke University in 1995, Robert Fine made a dramatic switch in the direction of his research. At Duke he studied the basic biochemistry of cancer cells. But he yearned for more.

Basic research “is important because it elucidates the truth in science and nature, but it will probably never affect a person’s life,” he says. “I found it very difficult to take cases of patients and get involved and get close to them and watch them die of a disease you can’t do much about.”

So Fine switched his emphasis, devoting his time to bridging the gap between his two passions: “finding a truth in nature which is almost like a religious experience,” and “relieving human suffering.”

His “translational” research has been having an impact ever since on patients suffering from some of the most intractable forms of cancer, such as pancreatic and tumors that are thought to be untreatable.

Traditionally, says Fine, pharmacological therapies have been based largely on inflexible specifications spelled out by the pharmaceutical companies that have developed then. Fine prefers to take those available drugs and design his own chemotherapies, testing them out in his laboratory before administering them to directly to patients.

“What we learned is that when you rationally design chemotherapies in the lab, you can make new treatments much more efficaciously and with less toxicity,” he says, “if you build them to be biochemically synergistic.”

By combining previously used cancer drugs in new ways and first testing them out in laboratory tissue cultures, for instance, Fine has developed a drug regime for advanced metastatic pancreatic cancer that has appears to have one of the highest response and survival rates in the US and Europe. The regime has been tested on hundreds of patients and still needs to be tested in Phase 3 clinical trials. 

But Fine has also recently received patents for altogether new treatments. Recently Fine and his researchers developed a small peptide that binds to mutated forms of the T-53 protein – a tumor suppressant that when mutated is found in about half of all malignant cancer tumors.  

Fine’s peptide acts like a scaffold, binding to the p-53, pushing it back into a “functional normal state” and automatically killing any cells that contain it.

“When it’s not mutated, P-53 turns on genes that will kill cells, so high levels of normal p-53 will kill cancer cells without chemotherapy,” Fine says. “We are extremely excited about this. We’ve tested it  in three different animal models and it works very well in animals carrying human cancer. We think it will work very well as a preventative measure. It is only thing that can kill precancerous cells, currently nothing kills them outside surgery.”

Fine and his lab have also developed a new way of delivering gene therapies, which have largely been spurned in the last decade because of concerns over their safety. Fine’s invention delivers gene therapy through a virus that causes colds, but has two “fail safes” that will only allow the therapy to “turn on” in cells that have mutant P-53 cells and another  mutated component only found in cancer called “mutant RAS.” 

“Because it’s in a cold virus, it will get inside the DNA of a person and it will not turn on in non-malignant cells,” Fine says. “We bent over backwards to make this so safe and tested it in four different animal models and it’s extraordinarily potent and useful in tumors with those two characteristics.”

To view technologies from Dr. Fine's lab, please click here