By Sue Rochman
From Mice to Men
The scientific method can help you decide if the latest cancer news is really news
By Sue Rochman
A Pedantic Process
Scientific discovery involves a glimmer of an idea, followed by years of hard work. In cancer research, these creative sparks often result in the identification of a new target—a gene or a protein or a cellular change that is driving the cancer cell.
It is common for the news media to report about novel cancer targets. And “it is important for people to know that basic science is making advances,” so that they support this work, says oncologist Beverly Mitchell, the deputy director of the Stanford Cancer Center at the Stanford University School of Medicine in California. But, she says, the public also needs to understand that finding a target is only the beginning of a long process.
Scientific methodology is like a pyramid. At the bottom—the first and largest layer—is the hypothesis. A hypothesis might go something like this: Drug A will latch on to protein B and disrupt tumor growth. If the hypothesis receives funding, the researcher will be able to move to the next level of the pyramid, which involves testing the drug on cancer cells in a laboratory. Success here will allow the researcher to move to the next step: testing the drug in animals—typically mice or rats that have been bred to develop cancer or are injected with cancer cells. The next three layers of the pyramid are the phase I, phase II and phase III clinical trials, which test drugs in humans.
Both cell studies and animal studies can illuminate how a drug works. Animal studies, in particular, are also useful for identifying potential toxic effects, explains oncologist Sridhar Ramaswamy, a cancer researcher at the Massachusetts General Hospital Cancer Center, in Boston. But, he underscores, neither of these types of studies “can predict what will happen in humans. … That information can only be learned in human trials.”
“A phase I trial can tell you if the drug will hurt the liver or kidney or other organs and it may give some indication of activity,” explains Ramaswamy. “But only in a phase II trial do we start getting true clues about effectiveness.” And only in a phase III randomized trial (or in certain phase II trials) do researchers learn if a drug is truly more effective than other drugs currently being used. That’s because a randomized study includes hundreds or even thousands of patients who are randomly assigned—often by a computer—to the different treatment options being compared in the trial. This allows researchers to see if the drug’s ability to slow or stop tumor growth that was observed in a small phase II trial is real or may have just occurred due to chance.
This “very prescribed set of steps” needed to develop a drug can take up to a decade, or longer, to complete, says Ramaswamy. Not all of that time is dedicated to the primary steps—scientists must also replicate their findings as they travel up the scientific pyramid. Frequently, scientists in other labs will try to reproduce the results of cell or animal studies, or clinical trial investigators will test a drug in new populations of patients. This ensures that the studies were done right, that the results were not a fluke, and that they hold true for different groups of people. It also enables a broader assessment of risks and benefits. When replication leads to conflicting results, even more studies are done.
It is their familiarity with the research pyramid that helps scientists interpret the cancer research studies that the media cover. The pyramid can help consumers as well. Reading about a cell study? Think: Let’s see what happens in animals. Reading about an animal study? Think: Let’s see what happens in humans. Phase I studies look promising? Great. Let’s look at phase II and phase III.