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Even as cancer therapies improve, basic questions about drug resistance, tumour spread and the role of normal tissue remain unanswered
BRENDAN MONROE
In 1996, Charles Sawyers designed early clinical trials for one of the first drugs aimed at a cancer-specific genetic mutation. The drug was imatinib, the cancer was chronic myeloid leukaemia and Sawyers a clinical oncologist at the Memorial Sloan Kettering Cancer Center in New York saw patients who had been debilitated by the disease rapidly improve when given the medicine. It was unbelievably satisfying, he says.
Unfortunately, he then saw many of those cancers come roaring back as they became resistant to the drug.
The experience with imatinib has given cancer biologists mixed messages. The medicine, now marketed by Novartis in Basel, Switzerland, as Gleevec or Glivec, highlights the potential of personalized medicine. Figuring out what mutation caused the disease and designing a drug to target it was a technological triumph, and it was followed by two further drugs to combat the emerging drug resistance.
But treating cancer by chasing mutation after mutation with drug after expensive drug is not a sustainable model not least because few cancers other than leukaemia have simple, known genetic causes. When we know the mutations and can get to a treatment strategy it's exciting, says Sawyers. But so far in the age of gene sequencing, he adds, we've grabbed the low-hanging fruit.
Biologists now know a huge amount about cancer much more than they did even ten years ago. About 500 genes have been implicated in the disease, and the list is growing. There are also about 100 approved cancer drugs, some of which, like imatinib, specifically target mutations in those genes, on top of older therapies such as surgery and radiation.
But all this knowledge is not enough: even in countries where people have access to the newest therapies, improvements in death rates have slowed. Up to half of cancers could be prevented by changes in diet and exercise, encouraging people to stop smoking and eliminating environmental risks such as pollution, but other gains will be harder. To conquer cancer, researchers will need to answer some basic scientific questions. Here, Nature looks at three of the most pressing.
How Can Drug Resistance be Overcome? To combat resistance, researchers are studying the cancer genome, coming up with new ways to design drugs, concocting combination therapies and even looking back to Darwin's theory of evolution.
More here:
Biology: Three Known Unknowns