In cancer science, many "discoveries" don't hold up

A former researcher at Amgen Inc has found that many basic studies on cancer - a high proportion of them from university labs - are unreliable, with grim consequences for producing new medicines in the future.

During a decade as head of global cancer research at Amgen, C. Glenn Begley identified 53 "landmark" publications - papers in top journals, from reputable labs - for his team to reproduce. Begley sought to double-check the findings before trying to build on them for drug development.

Result: 47 of the 53 could not be replicated. He described his findings in a commentary piece published on Wednesday in the journal Nature.

"It was shocking," said Begley, now senior vice president of privately held biotechnology company TetraLogic, which develops cancer drugs. "These are the studies the pharmaceutical industry relies on to identify new targets for drug development. But if you're going to place a $1 million or $2 million or $5 million bet on an observation, you need to be sure it's true. As we tried to reproduce these papers we became convinced you can't take anything at face value."

The failure to win "the war on cancer" has been blamed on many factors, from the use of mouse models that are irrelevant to human cancers to risk-averse funding agencies. But recently a new culprit has emerged: too many basic scientific discoveries, done in animals or cells growing in lab dishes and meant to show the way to a new drug, are wrong.

Begley's experience echoes a report from scientists at Bayer AG last year. Neither group of researchers alleges fraud, nor would they identify the research they had tried to replicate.

But they and others fear the phenomenon is the product of a skewed system of incentives that has academics cutting corners to further their careers.

George Robertson of Dalhousie University in Nova Scotia previously worked at Merck on neurodegenerative diseases such as Parkinson's. While at Merck, he also found many academic studies that did not hold up.

"It drives people in industry crazy. Why are we seeing a collapse of the pharma and biotech industries? One possibility is that academia is not providing accurate findings," he said.

BELIEVE IT OR NOT

Over the last two decades, the most promising route to new cancer drugs has been one pioneered by the discoverers of Gleevec, the Novartis drug that targets a form of leukemia, and Herceptin, Genentech's breast-cancer drug. In each case, scientists discovered a genetic change that turned a normal cell into a malignant one. Those findings allowed them to develop a molecule that blocks the cancer-producing process.

This approach led to an explosion of claims of other potential "druggable" targets. Amgen tried to replicate the new papers before launching its own drug-discovery projects.