Cancer immunotherapy looks to brighten future for aging society

As the risks of cancer increase among Japan's aging population, immunologist Tasuku Honjo is pinning his hopes on cancer treatments that shift the paradigm from traditional approaches directly targeting cancer cells to ones that stimulate the body's immune system to fight the disease.
Nobel laureate Honjo, 77, believes his research can help bring about a cure -- or at least turn cancer into a nonfatal chronic disease -- while the jury is still out on whether immunotherapy can become a first-line treatment option.
"Certain types of cancer patients are finally being cured thanks to immunotherapy. So I hope the percentage of such cases will steadily increase along with improvement (in the treatment)," Honjo said in a recent interview with Kyodo News.
"Even if tumors are not completely eliminated, people can survive as long as cancer is kept in check at a level where people can coexist with the disease," he said on the sidelines of an event in Yokohama arranged by Nobel Media in collaboration with the Japan Society for the Promotion of Science.
The discovery of the protein called PD-1 by Honjo and his team in 1992 has led to the development of the drug Opdivo, an immune checkpoint inhibitor that can trigger the immune system to attack cancer cells by targeting and blocking PD-1.
Honjo was jointly awarded the 2018 Nobel Prize in physiology or medicine for his contribution to cancer therapy in which he showed how the protein he discovered could function as a brake on the immune system. His fellow recipient, American immunotherapy scientist James Allison, was recognized for his study of another braking molecule.
A distinguished professor and deputy director general of the Kyoto University Institute for Advanced Study, Honjo gave a lecture and took part in a discussion with other Nobel laureates during the latest Nobel Prize Dialogue held in Japan under the theme of "The Age to Come," in which a number of policy makers, researchers, students and the general public took part.
"To discuss aging populations is a highly topical theme, especially in a Japanese context as the country is experiencing an extreme demographic shift," Laura Sprechmann, acting CEO of Nobel Media said in a statement.
The aging of populations is a global phenomenon, rather than something unique to Japan but the country reached the highest level in the ratio of aging among major countries in 2005, according to government data.
As of Oct 1, 2017, the number of people 65 or over stood at 35.15 million and accounted for 27.7 percent of the country's total population of 126.71 million, according to the 2018 Japanese government's Annual Report on the Aging Society. Japan's aging population is expected to continue to grow.
Cancer is often considered an age-related disease as numerous studies indicate that the risks of developing cancer increase with aging due to accumulated genetic mutations, among other factors, such as deteriorating immunity linked with growing old.
As we age, the thymus gland, which produces T cells that kill dysfunctional cells or foreign agents, shrinks, thus leaving humans more susceptible to infections and cancers.
But Honjo said he can one day imagine a scenario where people, particularly the elderly, can live their lives normally without pain despite having cancer.
"If we live to be old enough, there won't be any serious problem even if we have some tumors in our bodies," he said during his lecture.
He highlighted three strong points of immunotherapy, which developed from his discovery of PD-1.
First of all, he claims his treatment, "has the potential to be effective against all cancers."
"It also causes relatively less pain to patients" compared with other cancer treatments, pointing out that normal cells are not affected by immunotherapy.
"Thirdly, it can bring a complete cure," Honjo said, stressing that cancer did not reoccur in some patients even after they stopped receiving the therapy. He said there are many cases in which patients had no recurrence of cancer for five years.
According to Honjo, PD-1 blockade therapy has been approved for treating over a dozen different cancers.
Those cancers approved for the treatment between 2014 and 2018 include melanoma, lung cancer, and colorectal cancer, as well as all highly mutated cancers, regardless of the organ they originate from.
"The (PD-1 blockade) therapy is particularly effective against highly mutated cancers. It is a very significant (feature)...that we became able to treat various types of cancers that exceed a certain level in mutations with the therapy," Honjo said.
Naturally, patients will react differently to immunotherapy based on differences in their immune response, he said.
He noted raising the response rate of patients to the PD-1 blockade therapy is one area for improvement aimed at making the therapy a first-line treatment option, adding studies are still under way to figure out what types of patients respond the best.
There are also some immune-related adverse events to immunotherapy, although those side effects are less severe than with traditional cancer treatments, he said, citing a lack of knowledge about immunity among the reasons why adverse effects might be overlooked.
Common symptoms of side effects include fatigue, skin rashes, and diarrhea.
"The education of doctors is a major issue that needs to be addressed," he said.
He also expressed concerns over the future of basic science research in Japan, saying it is essential to create an environment where young researchers, especially in their 30s, can more freely engage in research they wish to pursue.
"These days, the ratio of young people advancing to graduate schools is declining and it is very concerning," he said.
According to data of the Education, Culture, Sports, Science and Technology Ministry, the ratio of people advancing to PhD programs has been declining in recent years.
"There should be a system to provide a sufficient amount of money that they can use freely for a long time," he said.

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