Annual Report 2022
Division of Translational Genomics (Kashiwa Campus)
Susumu S. Kobayashi, Akihiro Ohashi, Tomoko Yamamori, Ryo Kamata, Jie Liu, Chiaki Mashima, Yuta Sakae, Hitioshi Saito, Kei Oguchi, Misato Kamii, Takehiro Nakao, Toyohiro Yamauchi, Gaku Yamamoto, Masayo Mishima, Hiroko Nagayama
Introduction
The Division of Translational Genomics was restructured and the current division started when Susumu Kobayashi was recruited to the NCC in April 2018. We closely collaborate with intramural and extramural clinicians and researchers to develop genome biomarker diagnostics, explore rational molecular targets for anti-cancer therapies, and elucidate the molecular mechanisms of tumorigenesis, progression, and therapeutic responses. Kobayashi, who served as chief of the division in a cross-appointment with Harvard University, resigned at the end of this fiscal year.
The Team and What We Do
Our main goal is to conquer cancers, and we work hard to achieve it. In addition to our weekly laboratory meetings, we have combined weekly meetings with the Division of Translational Informatics. We also participate in center-wide research meetings and invite outside speakers to present the most up-to-date science.
Research Activities
For the past decade, molecular-target drugs have been game-changers for cancer therapeutic strategies. In most cases, however, these therapies fail due to intrinsic and acquired drug resistance. Our projects involved studying mechanisms of action and resistance mechanisms of resistance to EGFR tyrosine kinase inhibitors (TKIs) in lung cancer using multi-omics analyses, single cell analyses, mathematical modeling, and chemical biology. In collaboration with pharmaceutical companies, we evaluated several novel EGFR TKIs in lung cancer patients with EGFR exon 20 mutations. In addition, based on our discovery of a novel fusion gene, CLIP1-LTK in lung adenocarcinoma, we investigated mechanisms underlying its role in tumorigenesis and resistance to LTK inhibitors. Our long-term goal is to discover the target molecules for novel drug development to cure cancers.
Clinical Trials
We have participated in several clinical trials to support the translational aspects of studies.
Education
We have accepted and trained the following trainees: Graduate students from the University of Tokyo, Hokkaido University, and the Jikei University School of Medicine; and physicians and residents of the National Cancer Center Hospital East. Our staff made several educational seminar presentations at the University of Tokyo.
Future Prospects
In collaboration with other divisions in the NCC, other institutions, and pharmacological companies, we will investigate the mechanisms of action and resistance to targeted therapies including immune-checkpoint inhibitors. We will also continue to investigate genomic instability in cancers and identify molecules that determine vulnerability. Our major goal is to identify and develop novel therapeutics to treat cancers through our research activities.