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Challenging focus of cancer research

Nobel Prize-winning geneticist wants more emphasis on spotting diseases in earliest stages, less on drugs

BY DELTHIA RICKS | STAFF WRITER

June 18, 2004

A rare contrarian surfaced last week at the annual meeting of the American Society of Clinical Oncology, a gathering that over the past 40 years has trained an increasingly glowing spotlight on new cancer drugs.

Dr. Lee Hartwell, a Nobel Prize-winning molecular geneticist, told attendees at the New Orleans conference that it's now time for drugs to take a back seat to the development of keener diagnostic tests.

Hartwell, head of the Fred Hutchinson Cancer Research Center in Seattle, challenged doctors and drug companies, saying diagnostic research has long been underfunded and overshadowed by a narrow focus on drug development.

It costs $1 billion, Hartwell said, to funnel a single cancer medication through the regulatory pipeline. For a fraction of that, he said, new diagnostics to spot cancers in their earliest stages ultimately could save more lives. Not one to mince words, Hartwell even wonders whether the National Institutes of Health is capable of getting diagnostics on more agendas.

Early detection touted

An institutes spokeswoman, contacted on the issue, pointed to the agency's Early Detection Research Network, a consortium searching for "biomarkers" or gene mutations to be used in new diagnostics. Hartwell wants broader commercial cooperation. He said evidence demonstrates that cancer screenings save lives.

"The Pap smear strongly reduces mortality through early detection of cervical cancer as does colonoscopy for colon cancer. We know that early detection can work. What we need are cheap and effective diagnostic tests for more types of cancer," Hartwell said.

He would like to see gene-based diagnostics and is particularly interested in the emerging science of proteomics to find patterns of proteins that signal cancer's presence.

Hartwell told the standing-room-only crowd that virtually all forms of cancer can be cured with drugs now on the shelf if better diagnostics are developed.

"I am optimistic that we have the knowledge, science and technology to greatly improve outcomes for cancer in a relatively short time frame, but I am cautious because I don't know if we have the ability to organize the effort," he said.

Days later in an interview, he remained steadfast. "If you can achieve early detection, then current methods of treating cancer can cure cancer. I think the big benefit is in diagnosis."

Two halves of a whole

But Dr. Larry Norton, deputy physician in chief for breast cancer programs at Memorial Sloan-Kettering Cancer Center in Manhattan, said cancer drugs and diagnostics are "two sides of the same coin."

Norton is former president of the American Society of Clinical Oncology. He said screening may be developed, while treatment remains elusive.

Norton describes Hartwell as one of the world's top scientists, but added that scientists tend not to think like physicians. "Lee's a friend of mine. He's a classic scientist and scientists are very linear thinkers," Norton said. "In the history of medicine, things haven't always proceeded in a predictable way."

Yet most forms of cancer don't even have diagnostic tests, Hartwell emphasized, and few existing tests are precise enough. He also took a dim view of the meager gains in life expectancy from the new billion-dollar drugs.

"When the best talks at ASCO are about improving survival by two months," Hartwell told Newsday, "we've really got to do something else."

Hartwell won the Nobel Prize in medicine three years ago for unmasking the genes involved in cell division.

At the conference, the focus clearly is on drugs. The companies' exhibit area is like a carnival, enticing doctors with free espresso, candy, bottled water and personally engraved pens. Genentech, maker of the high-tech cancer drug Avastin, had a contraption nearly one story high from which a mist fell like a waterfall. The mist contained a faint but gargantuan double helix.

Mary Lynn Carver, spokeswoman for AstraZeneca, makers of the lung cancer drug Iressa, agrees development of diagnostics and medications are inseparable. "It's kind of a chicken-and-the-egg discussion."

Carver said Iressa, a targeted therapy, zeros in on the singular mechanism causing cancer cells to proliferate. Yet after the drug was prescribed to thousands, it was discovered "some people are super-responders and some are not." The same is true for other targeted drugs.

Studies show patients who respond have certain biomarkers. Now, screening tests are being developed to detect them. Carver added "even if the biomarker had been discovered first, we still would have had to do the drug discovery."

Dr. Soonmyung Paik, director of pathology at the National Surgical Adjuvant Breast and Bowel Project in Pittsburgh, said a cancer diagnostic is as difficult to develop as a drug.

As co-developer of OncoTypeDx, a gene-based diagnostic to predict a breast cancer recurrence, Paik reported on the test at the New Orleans conference. He found many doctors were not eager to offer the test to patients.

"They said they wanted to see more clinical testing," Paik said. The test, which cost about $20 million to develop, was federally approved in January.

A measure of support

Still, Hartwell's notion that cancer can be thwarted with drugs in existence got support in more ways than one at the conference. Research revealed that several existing drugs may have multiple applications.

Cholesterol-lowering statins may also prevent colorectal and prostate cancers, preliminary studies suggested. Taxotere, long used to treat breast cancer, may add a few months of life to men with late-stage prostate tumors.

Dr. Stuart M. Lichtman, director of geriatric oncology at North Shore University Hospital in Manhasset, said Hartwell is on the right track when calling for new treatments from medications already on pharmacy shelves. "One of the best examples of this is thalidomide," said Lichtman.Banned by the Food and Drug Administration in the early 1960s after it caused birth defects, thalidomide is now a cancer drug.

Hartwell insists economics is keeping diagnostics in the shadows. "There's not a big economic engine driving it," he said, "and the commercial sector won't get behind it because there's not a lot of money in it for them."