Annual Report 2018
Division of Translational Genomics (Kashiwa Campus)
Susumu S. Kobayashi, Akihiro Ohashi, Hiroshi Haeno, Mikiko Shibuya
Introduction
The new Division of Translational Genomics was restructured and 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 molecular mechanisms of tumorigenesis, progression, and therapeutic responses.
The Team and What We Do
Our dream is to conquer cancers, and we work hard to achieve this dream. In addition to our weekly laboratory meetings, we have combined weekly meetings with the Division of Translational Informatics. We also participate in the center-wide research meetings and invite outside speakers to present the most updated 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. We are interested in mechanisms of action and resistance mechanisms of resistance to EGFR tyrosine kinase inhibitors (TKIs) in lung cancer using multi-omics analyses, single cell analyses, and mathematical modeling. In collaboration with pharmaceutical companies, we evaluated several novel EGFR TKIs in lung cancer patients with EGFR exon 20 mutations. In addition, we have also started our research on genomic instability, one of the cancer hallmarks. We are interested in the mechanisms by which aberrant DNA replication and repair play crucial roles in tumorigenesis. Deeply understanding "Cancer Hallmarks and Vulnerability" is important to discover the target molecules for novel drug development.
Clinical trials
We have participated in several clinical trials to support translational aspects of studies.
We have accepted and trained the following trainees: Graduate students from the University of Tokyo and staff physicians and residents of the National Cancer Center Hospital East. We gave a few educational seminar presentations at the University of Tokyo.
Future prospects
In collaboration with other division in the NCC, other institutions, and pharmacological companies, we will investigate 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.
List of papers published in 2018
Journal
1. Ikemura S, Yasuda H, Matsumoto S, Kamada M, Hamamoto J, Masuzawa K, Kobayashi K, Manabe T, Arai D, Nakachi I, Kawada I, Ishioka K, Nakamura M, Namkoong H, Naoki K, Ono F, Araki M, Kanada R, Ma B, Hayashi Y, Mimaki S, Yoh K, Kobayashi SS, Kohno T, Okuno Y, Goto K, Tsuchihara K, Soejima K. Molecular dynamics simulation-guided drug sensitivity prediction for lung cancer with rare EGFR mutations. Proc Natl Acad Sci U S A, 116:10025-10030, 2019
2. VanderLaan PA, Rangachari D, Majid A, Parikh MS, Gangadharan SP, Kent MS, McDonald DC, Huberman MS, Kobayashi SS, Costa DB. Tumor biomarker testing in non-small-cell lung cancer: A decade of change. Lung Cancer, 116:90-95, 2018
3. Sridhar R, Takei H, Syed R, Kobayashi IS, Hui LB, Kamal A, Tenen DG, Kobayashi SS. Styryl Quinazolinones as Potential Inducers of Myeloid Differentiation via Upregulation of C/EBPalpha. Molecules, 23:2018
4. Jorge SE, Lucena-Araujo AR, Yasuda H, Piotrowska Z, Oxnard GR, Rangachari D, Huberman MS, Sequist LV, Kobayashi SS, Costa DB. EGFR Exon 20 Insertion Mutations Display Sensitivity to Hsp90 Inhibition in Preclinical Models and Lung Adenocarcinomas. Clin Cancer Res, 24:6548-6555, 2018