Genomics giant Nakamura redefines cancer:

TMU chair professor classifies genetic changes
so ‘we can attack at pinpoint’ instead of
targeting organ sites with identical treatments

Prof. Nakamura is Chair Professor in TMU’s Clinical Pharmacogenomics and Pharmacoproteomics program, and visits the campus regularly for guest lectures and the Prof. Yusuke Nakamura Scholarship Award Ceremony. He also leads 13 researchers at his University of Chicago laboratory.

Imagine a world without breast or colon cancer, without bone or blood cancers.

For Prof. Yusuke Nakamura, that world has arrived – because the most promising treatments focus not on the tumor’s location, but on the genetic changes that caused it.

This conceptual turnaround isn’t an academic abstraction limited to researchers. The real payoff is for patients, who can receive personally targeted immunotherapy treatments that are much more effective. The former standard of care was to prescribe the same toxic chemotherapy drugs for every patient at a standard “maximum tolerated dose” that in practice is barely tolerable for patients – and that becomes less effective with each course of treatment.

Prof. Nakamura spoke with TMU Spotlight this summer, but he’s used to the spotlight in terms of media coverage. He has for decades been a pioneer in cancer genomics, and his distinguished research career has yielded a thousand-plus publications as well as substantive advances in targeted treatments.

A few days before the interview, the Japan Times wrote an extensive profile on his early years as a cancer surgeon when despair spurred his passion for research, and on his reflections on different international research contexts.

And while he said he maintains his personal blog to keep his Japanese language skills sharp, his comments are even sharper. For example, a recent post concludes:

“It should be common sense to realize that doing immunotherapy after having weakened the patient’s immune system through chemotherapy will result in problems. I mean, it should be common sense; but Japan appears to be immune to this common knowledge. If you want to call your standard treatments ethical, you need to pay extra attention to whether your patients are elderly, or not willing to undergo chemotherapy. Those patients suffering from declining liver, kidney, or heart function become refugees from the cancer system. What can we do about this petrified health system?”

TMU is very fortunate to partner with this eminent scientist thanks to a Taiwanese former student, Prof. Wei-Chiao Chang, who created the master’s program at TMU after stints at Oxford University and RIKAN, the Japanese research powerhouse where the two worked together. (Prof. Chang is also profiled in this Spotlight issue.)

Here are Prof. Nakamura’s comments:

Q: What is the next big news in cancer research? Are there sweeping advances in treatment or understanding just around the corner?
A: Now the classification of cancer is increasingly not by organ, as in breast cancer or lung cancer. That doesn’t help anymore. Now the classification is done by the genetic changes. Actually that kind of clinical trial has started already.
Regardless of the organ, basically we screen for the mutation, and if a mutation is matched to certain drug, then we can provide that drug to any patient [who has the mutation].
Less than one month ago, the US FDA [Food and Drug Administration] approved one drug for cancers that have a genetic instability. Regardless of organ, and whether adult or children: it’s a new classification.
Pharmacogenomics is very important [in this conceptual shift]: because of it, we can view cancers according to their genetic changes. Now is the era of pharmacogenomics and pharmacogenetics, because we can select safer and more effective drugs by identifying these genetic changes. It’s a very strong tool to provide benefits to patients with cancer and other diseases.
All cancer drugs are toxins to cells, so high doses are required to kill cancer. But now we don’t need the maximum dose – we can attack at pinpoint [scale].

Q: What are the comparative advantages of doing research in Taiwan as opposed to the US?
A: The good thing in Taiwan is you have a registry for the drug prescriptions [through the National Health Insurance claims system database]. Also you have a monitoring system for all kinds of adverse drug events.
And, for example, TMU has 3000 beds [in three hospitals], so lots of clinical material is available there. So compared to Taiwan … for example, the University of Chicago Hospital has only 600 beds. Although we have affiliated hospitals, in general the hospital sizes in Taiwan are much bigger.

Q: How is Taiwan ready to be a leader in pharmacogenomics?
A: Because it has a homogeneous population. By comparison, the United States is very heterogeneous – we have quite different genetic backgrounds, particularly in Chicago, which seems to have a very diverse mix. To do pharmacogenomics, if populations are very diverse it’s difficult to get something important [in terms of research results].
Also, I was very impressed by TMU’s internationalization. For example, Dr. Chang’s laboratory is quite heterogeneous: people from Malaysia, people from India, from some African countries.
This is very important — because I think young scientists should be exposed to other cultures and other countries. We need to learn from each other. We need to understand our heterogeneity and differences.
For example, I think Taiwan is the leading country for [research on] drug hypersensitivity, particularly skin match. The relation to the genomic factor for drug hypersensitivity was found in Taiwan. This is very important, because these reactions are sometimes very lethal.
One type of skin hypersensitivity is called Stevens-Johnson syndrome – one third of such patients die. Taiwanese scientists found the connection between the drug and HLA, human leukocyte antigen.
And now they are using genetic tests to avoid drug hypersensitivity. [Taiwan is leading here] because of the registry of severe adverse reactions caused by drugs. That Taiwan has a registry – this is very important!
Here is an example of what we found. When breast cancer patients receive hormone therapy, one of the most commonly used drugs is tamoxifen, an estrogen receptor antagonist that works by blocking the estrogen pathway.
But tamoxifen itself is not a drug. Our bodies add OH, oxygen and hydrogen, at the end – and then it becomes the active [drug] form.
Twenty percent of Asians cannot convert tamoxifen to the active form, so for them it is useless and [leads to] higher incidence of recurrence. If we can pick out those kinds of patients, we can provide alternative drugs.

Q: Would you advise students to seek training in both clinical medicine and research, following your example?
A: I think it’s better to be exposed to clinical medicine [as well as research methods] because then we can learn what the patients suffer from.
Medical science seeks to solve the problems patients have. We need to learn what the problems are, [and] what the patients want to do. For example, I worked as a surgeon and I operated on cancer patients.
There are many questions, but the most simple question is … why a normal cell is converted to a cancer cell. [Another question is why] the growth rates of cancer are quite different, individual by individual. Some cancer patients die very quickly, but some patients even at advanced stages can survive for two or three years. Some patients responded well to a drug, but some patients had no benefit and some suffered from severe adverse reactions that sometimes kill cancer patients.
So these are our natural questions, if we face the patient. To keep motivation high for many years, we should do science for others, we should do science for patients. From my experience, I believe so. My mother died of colon cancer too – this is my strong motivation to fight against cancer.

Q: Can you comment on Taiwan’s progress toward globalization?
A: I think that already Taiwan is more international than Japan, because the majority of master’s students [in the TMU program] came from outside of Taiwan; in Japan, [international students are] rather limited.
Of course, the United States is more international, but Taiwan’s system is very well-adapted to internationalization. Education is done in English – it’s excellent! A mixture of cultures is needed to stimulate young people. And [Taiwan students] are very nice, and very diligent.

Q: Could you comment on the US scientific research system?
A: Because I have a Japanese heritage, I feel there’s too much freedom … because we need to have some experience to learn science. After exposure to some experience, then we can become independent.
Medicine is borderless. This is important: it doesn’t matter whether a patient is in China, Taiwan or Japan. If we find something important, we can provide medicines to all kinds of patients, regardless of countries.

Q: Do you have advice for young researchers?
A: I think students need to be exposed to high-level scientists. So I’m trying to teach them not only about science, but also how they should think about their future, how they should contribute to patients. This is my role: to encourage young people to move on.

For interviews or a copy of the paper, contact Office of Global Engagement via