Report on the use of non-clinical studies in the regulatory evaluation of oncology drugs

Yoshihiro Hayakawa; Manabu Kawada; Hiroyoshi Nishikawa; Takahiro Ochiya; Hideyuki Saya; Hiroyuki Seimiya; Ryoji Yao; Masahiro Hayashi; Chieko Kai; Akira Matsuda; Tomoki Naoe; Atsushi Ohtsu; Taku Okazaki; Hideo Saji; Masataka Sata; Haruhiko Sugimura; Yuichi Sugiyama; Masakazu Toi; Tatsuro Irimura

doi:10.1111/cas.12857

Report on the use of non-clinical studies in the regulatory evaluation of oncology drugs

Cancer Sci. 2016 Feb;107(2):189-202. doi: 10.1111/cas.12857.

Authors

Yoshihiro Hayakawa^{1

2}, Manabu Kawada^{1

3}, Hiroyoshi Nishikawa^{1

4}, Takahiro Ochiya^{1

5}, Hideyuki Saya^{1

6}, Hiroyuki Seimiya^{1

7}, Ryoji Yao^{1

8}, Masahiro Hayashi^{1

9}, Chieko Kai^{1

10}, Akira Matsuda^{1

11}, Tomoki Naoe^{1

12}, Atsushi Ohtsu^{1

13}, Taku Okazaki^{1

14}, Hideo Saji^{1

15}, Masataka Sata^{1

16}, Haruhiko Sugimura^{1

17}, Yuichi Sugiyama^{1

18}, Masakazu Toi^{1

19}, Tatsuro Irimura^{1

20}

Affiliations

¹ Subcommittee on Non-clinical Studies, The Science Board to the Pharmaceuticals and Medical Devices Agency, Tokyo, Japan.
² Division of Pathogenic Biochemistry, Department of Bioscience, Institute of Natural Medicine, University of Toyama, Toyama, Japan.
³ Institute of Microbial Chemistry, Microbial Chemistry Research Foundation, Numazu-shi, Japan.
⁴ Division of Cancer Immunology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan.
⁵ Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
⁶ Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo, Japan.
⁷ Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
⁸ Division of Cell Biology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
⁹ Department of Pharmacy, Toranomon Hospital, Tokyo, Japan.
¹⁰ Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
¹¹ Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
¹² National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
¹³ Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan.
¹⁴ Division of Immune Regulation, Institute for Genome Research, Tokushima University, Tokushima, Japan.
¹⁵ Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
¹⁶ Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
¹⁷ Department of Tumor Pathology, Hamamatsu University School of Medicine, Shizuoka, Japan.
¹⁸ Sugiyama Laboratory, RIKEN Innovation Center, RIKEN Cluster for Industry Partnerships, Kanagawa, Japan.
¹⁹ Department of Breast Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
²⁰ Juntendo University School of Medicine, Tokyo, Japan.

Abstract

Non-clinical studies are necessary at each stage of the development of oncology drugs. Many experimental cancer models have been developed to investigate carcinogenesis, cancer progression, metastasis, and other aspects in cancer biology and these models turned out to be useful in the efficacy evaluation and the safety prediction of oncology drugs. While the diversity and the degree of engagement in genetic changes in the initiation of cancer cell growth and progression are widely accepted, it has become increasingly clear that the roles of host cells, tissue microenvironment, and the immune system also play important roles in cancer. Therefore, the methods used to develop oncology drugs should continuously be revised based on the advances in our understanding of cancer. In this review, we extensively summarize the effective use of those models, their advantages and disadvantages, ranges to be evaluated and limitations of the models currently used for the development and for the evaluation of oncology drugs.

Keywords: Animal model; cancer; drug development; oncology drug; regulatory science.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Antineoplastic Agents
Disease Models, Animal*
Drug Discovery / methods*
Humans
Medical Oncology / methods*
Neoplasms*

Substances

Antineoplastic Agents