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INTERVIEW / At the launch of the program / Tetsuo Noda

Q: The two pillars of the program are the "development of innovative cancer therapeutic seeds" and the "development of cancer clinical seeds." Why were they chosen?

Noda: Most of the new cancer drugs launched on the market in recent years were developed by Western companies. The reason for this is that, although Japan has produced some outstanding results from basic research, there are almost no bio-venture organizations in Japan that can nurture the results of this research and transfer them to pharmaceutical companies.

The Group for Development of Innovative Cancer Therapeutic Seeds, therefore, selected five research areas in which excellent results have been obtained from basic cancer research and put together a team comprising a small number of researchers to carry out research and development. At the same time, the various essential support systems have been organized to develop excellent results (seeds) into basic materials for cancer therapeutic drugs (leads) on behalf of bio-venture organizations. This means that the entire process from discovering innovative seeds to screening substances that could become drugs is integrated and, thus, more efficient.

At the same time, Japan also has a very high level of clinical cancer research, and various types of valuable samples have been accumulated. Detailed examination of these samples using genomic analysis and other advanced analytical techniques may make it possible to discover seeds of biomarkers predicting the efficacy of drugs, new cancer therapies, and diagnostic methods. This process, known as reverse translational research (R-TR), is very important in the development of actual therapeutic and diagnostic methods.

The Group for Development of Cancer Clinical Seeds, therefore, put together five teams that all carry out R-TR from different angles, and these teams are effectively promoting research through full support of the technical aspects, e.g., genomic analysis, and ethical aspects of research using clinical samples from patients.

Q: The main target of this program is intractable cancer, but what does that mean?

Noda: Cancer has enormous diversity. Advances in therapeutic drugs and surgical techniques have improved the five-year survival rates of many cancers, but there are still cancers for which effective therapeutic methods are difficult to develop, as represented by pancreatic cancer. Also, there are many cancers that may be relatively straightforward to cure initially, but there is no effective therapy if they recur or spread to another part of the body. These cancers are known as intractable cancers, and a major objective of this program is to develop therapeutic methods to achieve complete cure.

Q:Specifically, what sort of cancer drugs are you aiming to develop?

Noda: Most cancer drugs to date have worked by suppressing cancer proliferation, because cancer cells proliferate more rapidly than normal cells. In actuality, though, not all cells in cancerous tissue proliferate rapidly. At present, cancer drugs are mainly molecular-targeted drugs. This approach to cancer drugs focuses on differences in the natures of molecules (proteins synthesized based on the gene sequence) of cancer cells and normal cells, and the drugs target molecules specific to cancer cells to suppress their activity.

We aim to take this approach even further by focusing on new systems within cells that are important for cancer cells, but are not used by normal cells, in order to discover new molecular targets. Our strategy is based on a better understanding of the diversity and other dynamics of cancer coming from basic research, and I hope this strategy will enable us to discover effective molecular targets for intractable cancer. For example, no drugs have yet been developed to kill "cancer stem cells" thought to produce cancer cells, in addition to attacking proliferating cancer cells. We will therefore work on the research and development of drugs attacking cancer stem cells, in order to develop drugs that can cure cancer completely.

Q: What are innovative seeds? What support will you give to developing them?

Noda:The "molecular targets discovered through a better understanding of cancer" mentioned earlier are a very good example of innovative seeds. When we have a new molecular target, in order to develop it, we need a system that uses cells or animals to evaluate the target for anticancer drugs, as well as a system to verify the feasibility of the target of the anti-cancer drug and screen the candidates for the inhibitor, which most universities and public institutions do not have. So we have established the Technical Supporting Facilities providing these systems. In addition, we will search for pharmaceutical companies with which to collaborate on developing therapeutic drugs from the developed seeds, and we will assist in negotiations with these companies.

Q:What is the genomic analysis carried out in the development of cancer clinical seeds? What kinds of results are expected?

Noda: Genomic analysis basically means investigating the base sequence of genomic deoxyribonucleic acid (DNA) within a cell. For example, if a particular drug is effective against one type of cancer but not against another type, the base sequences of the genomic DNA of the two types of cancer are compared to find the differences in DNA sequences between them. If the region showing a different sequence is used as a biomarker, it makes it easy to determine the efficacy of drug administration in advance, so that ineffective drug administration can be avoided.

In addition, cancer emerges by an innate mutation in the DNA, or when a mutation in the DNA comes about by environmental factors. It is possible to build up a catalogue of cancer-causing mutations by comparing the genomic DNA of various cancer cells with that of normal cells, and new molecular targets can be found in this catalogue.

Q: How do you plan to support genomic analysis?

Noda: The research I have outlined above is now possible because genomic analysis technologies have recently advanced rapidly, so that large-scale analyses can be carried out at high speed. A device called a next-generation sequencer is used in these analyses, but these devices are still expensive, and operating them efficiently calls for various techniques, from sample preparation to data processing obtained from the analysis. We are therefore planning to install a next-generation sequencer in the Technical Supporting Facility, provide analysis of genomic sequences of cancer samples from the patients at the request of the clinical researchers, and then return the results to them.

Q: Do you think Japan will be able to catch up or overtake the West in the application of research results?

Noda: Understanding cancer will inevitably lead to controlling cancer. The time required from understanding cancer to controlling cancer is steadily decreasing; this is beneficial for us, because researchers in Japan have particularly excelled at understanding cancer, so I believe we have plenty of opportunity to catch up or overtake the West. We must at all costs avoid a situation in which foreign companies dominate the pharmaceutical market in Japan with cancer drugs developed from molecular targets and genomic analysis data obtained from Japanese people. We are up against stiff competition, but I hope that the members of this program will work together on their research, and I ask for the support and cooperation of the Japanese people.

(Posted March 2012)

Q: The organization of this program was expanded in FY2014. What changes in government policy were behind this?

Noda: The Japanese government started the Comprehensive 10-year Strategy for Cancer Control in 1984, and a new strategy to promote cancer research has been established every 10 years since then. Over this 30-year period, the driving point has shifted from research to measures against cancer. In addition, there have been areas in which there has not been complete cooperation from the ministries and agencies involved in promoting the program.

Given this situation, the "Expert Committee Related to the Direction of Future Cancer Research" investigated the future direction of cancer research and specific research topics, and its report was submitted in 2013. At the same time, the government was promoting the formulation of its Healthcare Policy, which aimed at a healthy, long-lived society together with economic growth. For this reason, the new 10-year Cancer Research Plan drawn up in March 2014 came under the government's Healthcare Policy.

In 2015, research and development related to the government's Healthcare Policy were reorganized and unified under the Japan Agency for Medical Research and Development (AMED). As a result of this, this program, which was launched in FY2011 as a five-year plan by the Ministry of Education, Culture, Sports, Science and Technology, was incorporated into the AMED in FY2015, the program's final year.

Prior to the launch of AMED, the relevant ministries and agencies joined and began some trials for each disease. Among such activities, this project played a role in one of these initiatives, the Japan Cancer Research Project, which aimed to speed up the application of cancer therapies.

This program carries out research and development to nurture seeds obtained from basic research up to the level available for clinical trials, etc., and it transfers the results to the Practical Research for Innovative Cancer Control which is managed by the Ministry of Health, Labour and Welfare. Of course, this program can also transfer results to private corporations. At the same time, samples that are obtained through clinical research carried out under the Practical Research for Innovative Cancer Control are returned to this program.

This framework is planned to continue after AMED is established in FY2015. The role of this program, which has been cultivated since the program's launch, will be maintained and further clarified after this program is incorporated into AMED. The program's organization was expanded in 2014 in response to these major changes in its external environment.

Q: In what specific ways has the organization been expanded?

Noda: First, the organization was expanded to accelerate the process of development of innovative cancer therapeutic seeds during the latter half of the program. The existing research subjects of the Group for Development of Innovative Cancer Therapeutic Seeds have developed seeds acting on molecular targets over the past three years, and as a result, many candidates for drugs--known as "True-Hits"--have been found. However, more active support is needed to develop these "True-Hits" into drugs and transfer them to private corporations within the remaining two years of the research and development period. For this reason, we have improved the Technical Supporting Facilities.

For example, a cancer drug can be more efficiently delivered to the target tissue if it can be coupled with a Drug Delivery System (DDS). Also, it is possible to examine the movements of minute amounts of a drug inside the body if a highly sensitive imaging technique is used. The Technical Supporting Facilities have been put in place based on these DDS and imaging techniques.

At the same time, two research teams each have been added to the Group for Development of Innovative Cancer Therapeutic Seeds and the Group for Development of Cancer Clinical Seeds, getting many new seeds from basic research. This brings us to a total of seven teams in each group. In addition, research subjects that are prospective and have the possibility to achieve derivation within two years have been added to the existing research teams. Furthermore, in recognition of the support needed during the latter half of the program, as mentioned before, the Group for Development of Drug Discovery Promoting Technologies has been newly established, with three research teams carrying out research and development. The total number of research subjects now comes to about 150.

This program will now be promoted under this expanded organization. We will make every effort to develop seeds that originate from basic research and deliver them to patients as drugs as soon as possible. I ask for your continued support and cooperation with this program.

(Posted March 2015)

Tetsuo Noda

Director, The Cancer Institute of the Japanese Foundation for Cancer Research

Dr. Noda graduated from Tohoku University School of Medicine where he received his PhD in medicine (Doctor of Medicine). He was an Assistant at the Kyoto University Institute for Virus Research, a Fellow at MIT Whitehead Institute, Director of the Japanese Foundation for Cancer Research and a member of the Department of Cancer Biology, Professor at Tohoku University Graduate School of Medicine, Dean of the Tohoku University Graduate School of Medicine, member of the United Centers for Advanced Research and Translational Medicine (ART), and President of the Japanese Cancer Association. Dr. Noda assumed his present post in April 2006. He has achieved many innovative research results in the analysis of carcinogenesis controlling genes using mutant mice and in important genes involved in the differentiation of cells in biological tissues.

P-DIRECT

P-DIRECT / Japanese Foundation For Cancer Research
 3-8-31, Ariake, Koto, Tokyo 135-8550, Japan