Neil Spector, M.D., has witnessed countless miracle drugs obliterate cancer with such force in the laboratory that they seemed destined to cure cancer in people.

But many a promising compound has been unexpectedly crippled by the body’s complex array of physiologic defenses, says Spector, a new face in the Duke Comprehensive Cancer Center.

“The drug may sit in the stomach like a brick, or the pill isn’t soluble, or the drug has a half-life of 10 seconds and the body metabolizes it before it reaches the cancer,” says Spector, an oncologist and cancer biologist. “The chances that a compound tested in humans will eventually be approved is only about one in a hundred.”

Spector, the former director of Exploratory Medical Sciences in Oncology at GlaxoSmithKline, wants to improve those odds for new anti-cancer drugs. He’s made the unusual move of switching teams from corporate America to join Duke’s cancer drug development team as the new director of Translational Research in Oncology. He will also serve as co-director of the Experimental Therapeutics Program in the cancer center.

“I see enormous opportunities for academic medical centers to leverage their intellectual property in the drug discovery market,” said Spector. “This shift will require academic medical centers to develop business acumen to accompany their scientific prowess.”

“Scientific advances in the laboratory rarely see the light of day as relevant therapies for patients because drug development is such an enormously complex process,” he said.

For example, the role of transcription factors in promoting the growth and survival of tumor cells is well established. But thus far, no one has successfully developed a drug that effectively targets these cellular proteins because it is an extremely challenging endeavor, he said.

From Discovery to Development
“Creating new drugs must be an iterative process where you go from lab to mouse to human and back again until you ensure that the drug is effective and viable,” Spector said.

Indeed, Spector’s new role is assessing whether a cancer discovery is “developable.” Can the discovery be matched with a drug that blocks its action? Can the drug be delivered in a viable form? What experiments must be performed to assess the drug’s practicality in humans?

Spector sees his role as facilitator and mentor, having successfully developed two important cancer drugs from the bench to the clinic and then guided them through Food and Drug Administration (FDA) approval.

“My role will be to leverage the tremendous wealth of basic research and clinical resources available at Duke toward the development of experimental therapeutics. My group will be poised to help investigators with research strategies that ultimately produce a therapy for patients,” he says.

Mixing Drug Companies, Academics
Duke scientists, in turn, will assume a more prominent role in drug discovery for drug companies, which are shifting away from research in favor of developing and marketing their drugs. Spector says pharmaceutical companies will increasingly rely on institutions like Duke to conduct the science behind their drugs.

“Academic medical centers are entrepreneurial in spirit and are heavy weights in scientific acumen, so I envision drug companies outsourcing the research to these institutions,” he said.

Drug research is high-risk, but it has a very low yield financially, precisely because so much time and money is spent that may fail to produce a viable drug, said Spector. Institutions such as Duke already invest their time and effort in basic science advances, so they are well positioned to assume the research role for pharmaceutical companies, he said.

“I see this model as the only way for drug development to occur in the future,” said Spector.

Discover, Screen, Tweak, Build
The first step, he said, is to match discoveries with potential cures. Scientists often discover proteins that appear to promote cancer growth or spread, but the discovery is not carried into action.

Spector envisions whisking these discoveries to chemists in a chemical screening facility that houses millions of different compounds. There, chemists will match the cancer-causing proteins with compounds that block their activity. Spector says outsourcing this task to large chemical screening companies can accelerate the process of matching cancer-causing molecules to potential drugs.

Once a match is determined, researchers can test the compound in animals to assess its viability, and then go back to the lab for tweaking. If promising, the drug can move forward, if not, it is quickly scrapped and a new protein can begin the screening process.

One by one, such compounds can build an arsenal of choices to battle individual cancers.

“We are getting away from the notion that all breast cancers, or all lung cancers, are the same,” Spector said. “Each has its own characteristics that need to be treated in a specific and targeted manner.”

“Clearly, there are critical wires in tumors that, if you cut, the lights will go out,” he said. “The key is to find the major wires that will shut down the cell, and turn those discoveries into viable drugs for patients.”