“It did not seem like too much to ask,” he recalled in a speech to the American Association for Cancer Research annual meeting in Chicago. “But I knew that wasn’t going to happen, not given the limited options for therapy we had.”
Sharpless’s frustration with the cancer treatments available in the late 1990s helped fuel his interest in basic research. He became a geneticist and molecular biologist — doing work on cell division and aging in mice — as well as a practicing oncologist.
Sharpless, who is 51, ended up running the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill. Six months ago, he became director of the National Cancer Institute, the largest institute of the National Institutes of Health. He took over at a time of rising hopes for new cancer treatments tempered by growing concerns about costs and widening health-care disparities.
“He is who we need now,” said Robert Vonderheide, director of Abramson Cancer Center at the University of Pennsylvania, who trained with Sharpless at Massachusetts General Hospital. “He clearly understands what the future of cancer is, and what we should do and what we should not do.”
For the past several months, Sharpless has been on a “listening tour” at NCI, talking to employees, patients, outside researchers and industry experts. Now he’s detailing his plans, beginning with his appearance in Chicago on Monday. Here’s what is on his mind, based on the speech and an interview with The Washington Post:
Cancer is hundreds, if not thousands, of diseases — and that changes everything. Cancer research and treatment today is being driven by the realization that the disease is made up of innumerable subtypes, all requiring their own therapies, Sharpless said. Lung cancer, for example, is probably more than 100 clinically distinct diseases. That “staggering heterogeneity,” he said, demands a new understanding of the biology of cancer, novel ways of conducting clinical trials, innovative approaches for harnessing data from patients, and ensuring that scientists have an array of skills, from immunology to data mining.
Clinical trials need to be overhauled. The way cancer drugs are tested is outmoded and inefficient, he said. The traditional trial — in which hundreds of patients are randomly assigned to one treatment arm or the other, and the results compared — doesn’t work for a fragmented field trying to deal with thousands of subtypes, he added.
Already, there is a shortage of patients for all trials — only 5 percent of adult cancer patients enroll in studies — and many studies don’t get off the ground. In addition, he said, the per-patient costs of trials are surging, driving up drug prices. And eligibility criteria, which determine which patients can enroll, could be loosened in many cases without hurting results, he said.
The NCI’s MATCH trial, in which patients are assigned to one of dozens of treatments based on genetic testing, is an example of a study with a modern design, he said. That trial has enrolled 6,000 patients at 1,100 sites across the country. Sharpless also said more trials should be conducted at community oncology practices across the country, where 85 percent of patients are treated, rather than mostly at academic medical centers.
Big Data needs to be harnessed — soon. Sharpless is passionate about using big data to understand, prevent and treat cancer, and especially in determining which therapies will work for which patients, given the underlying biology of their tumors. To do that, he said, scientists need to move from passive data sharing — putting data in the cloud and letting others use it — to data aggregation and analysis that would shed light on patient outcomes.
Such data aggregation, he maintained, will be able to answer questions ranging from the effect of diet and exercise on cancer risk to why some patients respond to old, usually ineffective drugs. And he said he is “100 percent convinced” that artificial intelligence and machine learning will be instrumental in finding and analyzing valuable data buried in electronic medical records and elsewhere.
Using basic science to tackle all cancers is critical. Sharpless said TV ads showing new treatments for melanoma or lung cancer “can feel like a fist to the stomach” if a loved one has pancreatic cancer or a brain tumor.
While researchers have made progress against some cancers, they have made almost no headway against others. “We cannot work on just the easy cancers or the common ones or the best-understood ones,” he said. “We have to work on all of them.”
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