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Division of Rare Cancer Research

Tadashi Kondo, Xiaoqing Pan, Rieko Ohki

Introduction

The research goal of the Division of Rare Cancer Research is to create the innovative seeds for better clinical outcomes for rare cancer patients. A rare cancer is defined as a cancer with incidence of less than six. Rare cancer includes approximately 200 cancer types, and despite the rarity of each rare cancer, they represent approximately 15% in total of all cancer cases in Japan. Thus, rare cancer research deals with wide-ranging subjects for a large number of cancer patients. Although themes of rare cancer research are quite general ones such as those for prevention, diagnosis, and treatment, as the research resources such as biobank materials and databases of rare cancers are limited, we need to make a special effort for rare cancer research. With this notion, the project to create fundamental tools for rare cancer research was launched in our laboratory. The establishment of the patient-derived cancer models, and the database for meta-analysis of genes are the efforts to solve problems of the limited amount of clinical material. Re-purposing of cancer drugs is a practical approach to rare cancer, and the experimental systems for re-purposing of cancer drugs were created in our laboratory. Those include the high-throughput screening system and the application of Connectivity Map and other bioinformatics modalities. Studies for individual rare cancer have also been conducted in our laboratory. Using global gene and protein data, we identified candidates of novel innovative seeds, e.g. predictive and prognostic biomarkers. Our experience and fundamental systems for rare cancer research will be applicable for major cancer research.

Research activities

1.Establishment of fundamental research system

*Patient-derived cancer models were created from the clinical materials of sarcoma patients.

*Screening system for the study of re-localization of cancer drugs was established and used for the cell panel.

*Platform of bioinformatics such as the original Connectivity Map was created and applied to the study of re-localization of cancer drugs.

*Database of gene status of rare cancer was created using bioinformatics approach.

2.Study of individual rare cancer

The identification of therapeutic targets and biomarkers was undertaken using clinical materials and our original cell panel. The biomarker candidates to predict the resistance of molecular anti-cancer drugs and those to evaluate the invasion potentials of tumors were identified by a multi-omics approach. Their molecular backgrounds and validation using additional cases are under consideration.

3.Reverse innovation

The research platforms were developed with the idea that they will be applicable to other malignancies.

Education

Two PhD students and three post-doctorate researchers were educated.

Future prospects

Our research activities will benefit patients with rare cancers. The fundamental system for rare cancer research will be applicable to the research of all cancers.

List of papers published in 2016

Journal

1.Ezawa I, Sawai Y, Kawase T, Okabe A, Tsutsumi S, Ichikawa H, Kobayashi Y, Tashiro F, Namiki H, Kondo T, Semba K, Aburatani H, Taya Y, Nakagama H, Ohki R. Novel p53 target gene FUCA1 encodes a fucosidase and regulates growth and survival of cancer cells. Cancer Sci, 107:734-745, 2016

2.Asano Y, Kawase T, Okabe A, Tsutsumi S, Ichikawa H, Tatebe S, Kitabayashi I, Tashiro F, Namiki H, Kondo T, Semba K, Aburatani H, Taya Y, Nakagama H, Ohki R. IER5 generates a novel hypo-phosphorylated active form of HSF1 and contributes to tumorigenesis. Sci Rep, 6:19174, 2016

3.Kondo T. Proteogenomics for the Study of Gastrointestinal Stromal Tumors. Adv Exp Med Biol, 926:139-151, 2016

4.Morofuji N, Ojima H, Hiraoka N, Okusaka T, Esaki M, Nara S, Shimada K, Kishi Y, Kondo T. Antibody-based proteomics to identify an apoptosis signature for early recurrence of hepatocellular carcinoma. Clin Proteomics, 13:28, 2016

5.Takai Y, Matsuo A, Qiao Z, Kondo T. Antitumor activities of BIBF 1120, BI 860585, and BI 836845 in preclinical models of sarcoma. Integr Mol Med, 3:755-760, 2016

6.Yamasaki H, Miyamoto M, Yamamoto Y, Kondo T, Watanabe T, Ohta T. Synovial sarcoma cell lines showed reduced DNA repair activity and sensitivity to a PARP inhibitor. Genes Cells, 21:852-860, 2016

7.Pan X, Yoshida A, Kawai A, Kondo T. Current status of publicly available sarcoma cell lines for use in proteomic studies. Expert Rev Proteomics, 13:227-240, 2016

8.Kubota D, Kosaka N, Fujiwara T, Yoshida A, Arai Y, Qiao Z, Takeshita F, Ochiya T, Kawai A, Kondo T. miR-125b and miR-100 Are Predictive Biomarkers of Response to Induction Chemotherapy in Osteosarcoma. Sarcoma, 2016:1390571, 2016