It's all well and good to read about advances researchers are making in cancer, but why does so little of that research translate to the clinic? At a panel discussion on the topic at ASCO this week, MD Anderson Cancer Center's Lee Ellis had a few ideas. For one thing, Ellis said, mice aren't people, so it's difficult to translate discoveries made in mouse models to human patients, because mouse tumors progress faster and the duration of therapy is shorter because they die quickly. Instead, Ellis suggested, researchers should use genetically-engineered mice that more accurately imitate the course of human cancers. But, he cautioned, mouse models shouldn't be abandoned, as another problem with cancer research is that scientists are sometime too eager to test combination therapies on humans, and skip the mouse tests altogether, leading to disappointment when the treatments don't work. We should never subject a human to a regimen that hasn't been tested on a mouse, he added. Another problem is that researchers sometimes use cell lines without really knowing what organ tissue they come from. Recent studies on three cell lines commonly thought to be esophageal cancer lines revealed the lines aren't esophageal tissue at all, Ellis said, leading to major setbacks to research done on those lines. Researchers need to validate their cell lines before working on them, he said.
Another point Ellis made was that a potential treatment needs to make a very big difference in a mouse study if it is to translate to meaningful differences for humans. There has been a lot of disappointment in Phase III studies because the difference a treatment makes in animal models hasn't been big enough to translate meaningfully to humans. Additionally, Ellis said, selective reporting of positive studies hurts the research community because there is value in negative data. Knowing what doesn't work in cancer can lead to information on markers of drug resistance or sensitivity, but as the scientific community has a bias toward positive results, these so-called negative findings are often buried. Ellis suggested that major journals provide forums for reporting negative data, and that companies who sponsor studies must allow the researchers conducting them to report all information, even if it isn't positive.
Finally, Ellis said, the current grant system is "cumbersome and slow" and doesn't encourage risky or innovative research. Reviews for funding take too long, and the processes in place to give researchers money require that they spend too much time filling out paperwork and answering questions from reviewers, Ellis added. The review process needs to be sped up, the people holding up the review systems need to be well-compensated, and the system needs to encourage risk and innovation, instead of the "me-too" drugs and trials that are becoming prevalent. The community needs to work together and make changes in order to see its work translate into fewer deaths in the clinic, Ellis said.