Tim Haystead, PhD
Written by Whitney L.J. Howell
Imagine being able to look at a cancer tumor and in seconds know – really know – whether it’s malignant. Ongoing work at Duke University could make this ability a clinical reality, adding a target-sensitive arrow to the quiver of treatments for breast and prostate cancer.
For nearly two decades, Duke researcher and faculty member Timothy Haystead, Ph.D., has tracked protein kinases – enzymes in the body that bind to and change other proteins – and the inhibitors that can deactivate them.
“It was a focused effort to find targets with varying degrees of selectivity and determine which targets were considered for diseases,” said Haystead, who is also an associate professor of pharmacology, cancer biology, and pathology. “We realized we could develop a clinical program, so we focused on compounds that we knew were clinical targets for cancer.”
As a result, Haystead founded Durham-based Serenex Inc. in 2000. Pfizer Inc. subsequently acquired the biotechnology company in 2008. It was Haystead’s discovery of the connection between a particular cancer target – Heat Shock Protein 90 (Hsp90) – and its inhibitor, SNX-5422, that led to the purchase.
Using affinity platforms that create pure kinases based on their specific binding characteristics, Haystead and his team identified inhibitors that go after nefarious enzymes present in tumors with pinpoint accuracy. After several rounds of investigation, the team made their discovery.
“When we put Hsp90 through the system, we found an extremely, exquisitely potent inhibitor,” he said.
Since then, SNX-5422, Hsp90’s orally-administered bioinhibitor, has completed Phase 1 clinical trials and continues its march to clinical use. So far, its efficacy has been significant. It’s an excellent strategy, Haystead said, to potentially cure patients rather than prescribe extended treatments. And, using a combination therapy to avoid long-term use of individual drugs could also prevent drug resistance.
“It actually stops tumors from growing. When the drug is present, the tumors stabilize,” Haystead said. “And, if Hsp90 is combined with another existing therapy, such as Herceptin for breast cancer, we can literally wipe out tumors.”
But Haystead’s work with Hsp90 didn’t stop when Pfizer absorbed his company and acquired the intellectual property. In 2010, armed with new molecules based on Hsp90, the team launched studies into whether the enzyme could be used in imaging studies for early identification of metastatic cancer. By attaching a fluorescent tracer to Hsp90, researchers are currently using PET scans to see which tumors take it in. High Hsp90 absorption, which can be seen by concentrated clusters of fluorescence in an image, correlates to great malignancy.
This type of strategy could prevent unneeded aggressive therapies for both breast and prostate cancer patients, he said. Tumors that are more benign can be treated with less intense methods.
“Everyone wants to find a metastasis earlier, and non-invasive imaging is an excellent way to do this,” he said. “The idea is that a patient would come in with a suspicious mass that the histology confirms is odd. You administer Hsp90, take a probe, and determine the tumor’s nature based on where and how much Hsp90 you see.”
Work is underway, Haystead said, to expand this imaging strategy for use in MRI scans, as well.
Hsp90’s usefulness might reach beyond cancer research and treatment, though. In collaboration with Barton F. Haynes, M.D., director of the Duke Human Vaccine Institute, Haystead’s team is investigating whether Hsp90 might also have a role in treating HIV. Initial results have shown that HIV-infected cells readily absorb Hsp90, making them easier to target.
“We’re excited at the prospect that you could take thoroughly safe drugs and immediately take them to clinical trials for HIV,” Haystead said. “It could either add to the growing repertoire of drugs for that disease or could help cure it.”
No matter the type of research – cancer or infectious disease – one of the biggest factors in his research success, he said, has been simply being at Duke. A synergy exists between all the facilities, institutes, and schools associated with the University that makes it nearly impossible to avoid innovation.
“At every level, from bench mechanics to animal studies to clinical applications, Duke offers the resources and personnel,” he said. “Taking something like our affinity platform with chemical things and translating that into a clinically-relevant setting doesn’t happen everywhere. That makes Duke unique among academic enterprises.”
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