Annual Report 2020

Division of Rare Cancer Research

Tadashi Kondo, Rei Noguchi, Yuki Yoshimatsu, Yooksil Sin

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 per 100,000 annually. 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. We consider that the fundamental problem of rare cancer research is a lack of the research resources such as cancer models, biobank materials and databases. We therefore address these issues. The establishment of the patient-derived cancer models, and the database for meta-analysis of genes are efforts to solve problems related to the limited amount of clinical material. Re-purposing of cancer drugs is a practical approach to rare cancers, and the experimental systems for re-purposing of cancer drugs were created in our laboratory. These 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 for novel innovative seeds, e.g., predictive and prognostic biomarkers. To facilitate the research and development of novel medical seeds, we have developed proteogenomics software. 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 a bioinformatics approach.

2. Study of individual rare cancers

 The identification of therapeutic targets and biomarkers was undertaken using clinical materials and our original cell panel. We identified the biomarker candidates to predict the resistance of molecular anti-cancer drugs as well as the ones to evaluate the invasion potentials of tumors, using 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

 Three PhD students and two post-doctral fellows were trained.

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 2020

Journal

1. Nakano Y, Takadera M, Miyazaki M, Qiao Z, Nakajima K, Noguchi R, Oyama R, Kimura Y, Okuhiro Y, Yamasaki K, Kunihiro N, Fukushima H, Inoue T, Hara J, Ozawa T, Kondo T, Ichimura K. Drug screening with a novel tumor-derived cell line identified alternative therapeutic options for patients with atypical teratoid/rhabdoid tumor. Hum Cell, 34:271-278, 2021

2. Noguchi R, Yoshimatsu Y, Ono T, Sei A, Hirabayashi K, Ozawa I, Kikuta K, Kondo T. Establishment and characterization of NCC-MFS2-C1: a novel patient-derived cancer cell line of myxofibrosarcoma. Hum Cell, 34:246-253, 2021

3. Noguchi R, Yoshimatsu Y, Ono T, Sei A, Hirabayashi K, Ozawa I, Kikuta K, Kondo T. Establishment and characterization of a novel cell line, NCC-TGCT1-C1, derived from a patient with tenosynovial giant cell tumor. Hum Cell, 34:254-259, 2021

4. Tsuchiya R, Yoshimatsu Y, Noguchi R, Sei A, Takeshita F, Sugaya J, Fukushima S, Yoshida A, Ohtori S, Kawai A, Kondo T. Establishment and characterization of NCC-DDLPS1-C1: a novel patient-derived cell line of dedifferentiated liposarcoma. Hum Cell, 34:260-270, 2021

5. Noguchi R, Yoshimatsu Y, Ono T, Sei A, Hirabayashi K, Ozawa I, Kikuta K, Kondo T. Establishment and characterization of NCC-LMS2-C1-a novel patient-derived cancer cell line of leiomyosarcoma. Hum Cell, 34:279-288, 2021

6. Noguchi R, Yoshimatsu Y, Sei A, Hirabayashi K, Ozawa I, Kikuta K, Kondo T. Establishment and characterization of NCC-MLPS1-C1: a novel patient-derived cell line of myxoid liposarcoma. Hum Cell, 34:667-674, 2021

7. Noguchi R, Yoshimatsu Y, Ono T, Sei A, Hirabayashi K, Ozawa I, Kikuta K, Kondo T. Establishment and characterization of NCC-PLPS1-C1, a novel patient-derived cell line of pleomorphic liposarcoma. Hum Cell, 34:688-697, 2021

8. Kito F, Oyama R, Noguchi R, Hattori E, Sakumoto M, Endo M, Kobayashi E, Yoshida A, Kawai A, Kondo T. Establishment and characterization of novel patient-derived extraskeletal osteosarcoma cell line NCC-ESOS1-C1. Hum Cell, 33:283-290, 2020

9. Oyama R, Kito F, Takahashi M, Hattori E, Noguchi R, Takai Y, Sakumoto M, Qiao Z, Toki S, Sugawara M, Tanzawa Y, Kobayashi E, Nakatani F, Iwata S, Yoshida A, Kawai A, Kondo T. Establishment and characterization of patient-derived cancer models of malignant peripheral nerve sheath tumors. Cancer Cell Int, 20:58, 2020

10. Yasukawa M, Ando Y, Yamashita T, Matsuda Y, Shoji S, Morioka MS, Kawaji H, Shiozawa K, Machitani M, Abe T, Yamada S, Kaneko MK, Kato Y, Furuta Y, Kondo T, Shirouzu M, Hayashizaki Y, Kaneko S, Masutomi K. CDK1 dependent phosphorylation of hTERT contributes to cancer progression. Nat Commun, 11:1557, 2020

11. Yoshimatsu Y, Noguchi R, Tsuchiya R, Kito F, Sei A, Sugaya J, Nakagawa M, Yoshida A, Iwata S, Kawai A, Kondo T. Establishment and characterization of NCC-CDS2-C1: a novel patient-derived cell line of CIC-DUX4 sarcoma. Hum Cell, 33:427-436, 2020

12. Yoshimatsu Y, Noguchi R, Tsuchiya R, Sei A, Sugaya J, Iwata S, Yoshida A, Kawai A, Kondo T. Establishment and characterization of NCC-SS3-C1: a novel patient-derived cell line of synovial sarcoma. Hum Cell, 33:877-885, 2020

13. Yoshimatsu Y, Noguchi R, Tsuchiya R, Sei A, Sugaya J, Iwata S, Sugiyama M, Yoshida A, Kawai A, Kondo T. Establishment and characterization of NCC-ssRMS1-C1: a novel patient-derived spindle-cell/sclerosing rhabdomyosarcoma cell line. Hum Cell, 33:886-893, 2020

14. Yoshimatsu Y, Noguchi R, Tsuchiya R, Sei A, Nakagawa M, Yoshida A, Kawai A, Kondo T. Establishment and characterization of NCC-DFSP3-C1: a novel patient-derived dermatofibrosarcoma protuberans cell line. Hum Cell, 33:894-903, 2020

15. Yoshimatsu Y, Noguchi R, Tsuchiya R, Sei A, Sugaya J, Fukushima S, Yoshida A, Kawai A, Kondo T. Establishment and characterization of NCC-ASPS1-C1: a novel patient-derived cell line of alveolar soft-part sarcoma. Hum Cell, 33:1302-1310, 2020

16. Sin Y, Yoshimatsu Y, Noguchi R, Tsuchiya R, Sei A, Ono T, Toki S, Kobayashi E, Arakawa A, Sugiyama M, Yoshida A, Kawai A, Kondo T. Establishment and characterization of a novel alveolar rhabdomyosarcoma cell line, NCC-aRMS1-C1. Hum Cell, 33:1311-1320, 2020

17. Noguchi R, Yoshimatsu Y, Ono T, Sei A, Hirabayashi K, Ozawa I, Kikuta K, Kondo T. Establishment and characterization of NCC-GCTB1-C1: a novel patient-derived cancer cell line of giant cell tumor of bone. Hum Cell, 33:1321-1328, 2020