A Japanese cancer-genomics pioneer targets new therapies.
As a young abdominal surgeon in Japan, Yusuke Nakamura saw more than one patient succumb to cancer. The disease’s savagery—and the lack of effective treatments—disheartened him, and he vowed to find solutions. Losing his mother to colon cancer further strengthened his resolve. His plan: analyze the human genome to create cancer-fighting drugs.
Over the past decade, Nakamura has pinpointed genes that are overexpressed specifically in cancer cells and has discovered dozens of molecules that may be viable targets for developing anticancer treatments. Yet for Nakamura, who joined the University of Chicago Medicine in April, those victories have turned bittersweet.
“Getting the results, I feel more and more guilty to Japanese patients,” he says, referring to a recent series of promising clinical trials for drugs he helped design. That’s because the trials aren’t taking place in Japan. Stymied by the government’s lack of support for translational research—which turns lab findings into real-world therapies—Nakamura had to take his work elsewhere. “It’s obvious,” he told Nature in February, “that support for genomics is not there.”
Such support had once been available. One of Japan’s genomic pioneers, Nakamura catapulted his country into the biomedical spotlight in 2005 as head of its International HapMap team, a global effort to identify common DNA sequence variations that could be useful for understanding diseases and developing treatments.
Under Nakamura’s direction, Japan produced roughly a quarter of the world’s data, outpacing every other participating country. Meanwhile, through the biotech company he founded in 2001, OncoTherapy Science, he aimed to translate the findings into treatments by targeting genetic variants linked to particular cancers.
When Nakamura was appointed secretary general of Japan’s Office of Medical Innovation in January 2011, it seemed an opportunity to apply his clinical expertise and entrepreneurial vision on a broader scale. By spearheading research in pharmacogenomics—the study of how genetics determine drug response—he hoped to usher Japan into an era of personalized medicine. Yet less than a year later, Nakamura resigned his cabinet post.
“I was asked by the former Japanese cabinet to make a national strategy for medical innovation,” he told the Chronicle of Higher Education this past January. “However, because of the terrible disaster by the [March 2011] earthquake, tsunami, and the subsequent nuclear-power-plant issues, the Japanese government could not commit to the long-term strategy.” At the same time, the government had shifted its focus toward more basic scientific research, into areas such as protein structure.
In April Nakamura left the University of Tokyo’s Human Genome Center and joined Chicago as a professor of medicine and deputy director of the Center for Personalized Therapeutics.
“To improve the quality of life for cancer patients, it is essential to establish personalized medicine,” says Nakamura. “That link between the basic science and clinical science is very tight at the University.”
Nakamura’s presence strengthens those ties. “Everyone who’s worked with him says he has the best genotyping in the world,” says center director and oncologist Mark Ratain, the Leon O. Jacobson professor of medicine. Starting in 2007, Nakamura and Ratain collaborated on a National Institutes of Health DNA sequencing project in which Nakamura’s Japanese team decoded the genetic makeup for several US patient samples. “No one had ever seen data of such high quality,” Ratain says.
At Chicago Nakamura will build on his track record of identifying drug targets. For example, after finding that a gene known as SMYD3 frequently appears in patients with colorectal and hepatocellular carcinomas, he and his team determined that knocking out the gene could stunt cancer-cell growth. Other therapies being developed include peptide vaccines, which induce an immune response to cancer cells.
Meanwhile, Nakamura’s OncoTherapy Science continues clinical trials. The company is testing a gastric-cancer drug in Singapore, and in Lyon, France, it has begun phase one trials for an antibody targeting synovial sarcoma, a rare soft-tissue cancer that typically afflicts the upper and lower extremities.
For Nakamura, promising outcomes in Lyon—the sarcoma drug has so far been effective with no adverse reactions—provoke mixed emotions. “Some Japanese patients have contacted us and asked why can’t we start clinical trials in Japan,” he says, troubled. “But the process there is very complicated, and there’s a very high hurdle to overcome.”
Joining Chicago has given him optimism, however. “Here doctors are waiting for new treatments,” he says. “Patients expect they will be given a new hope, new cures.” Eventually those promises may be delivered in Japan as well. As he told Nature in February, “By moving to the United States, I might be able to bring something back.”