Announcing the approval of the apolipoprotein A2 isoform index for in vitro diagnostics in Japan
June 12th, 2023
Nippon Medical School
National Cancer Center
Japan Agency for Medical Research and Development (AMED)
The C-terminal ends of amino acid sequences of apolipoprotein A2 homodimer consist of alanine (A), threonine (T), and glutamine (Q). The circulating forms of apolipoprotein A2 in the blood are cleaved at the C-terminal ends of the amino acid sequence.
Professor Honda (Nippon Medical School, Tokyo, Japan) and colleagues discovered the aberrant processing of the C-terminal ends of amino acids of circulating apolipoprotein A2 in the blood of patients with pancreatic cancer and individuals at high risk for pancreatic cancer.
Toray Industries, Inc. (Tokyo, Japan) obtained approval for in vitro diagnostics (IVD) for the detection of pancreatic cancer from the Ministry of Health, Labour and Welfare of Japan through collaboration with Nippon Medical School and the National Cancer Center (Tokyo, Japan), and with support from the Japan Agency for Medical Research and Development.
In Japan, 44,000 people were diagnosed with pancreatic cancer in 2019 and an estimated 38,000 deaths from pancreatic cancer were reported in 2020. This newly approved IVD for the detection of pancreatic cancer is a blood test. Since the test measures a substance different from existing tumor markers, it is expected to detect pancreatic cancer patients who cannot be detected with existing tumor markers.
Nippon Medical School and the National Cancer Center will continue to cooperate with all parties concerned to deliver diagnostic products to patients as quickly as possible.
This achievement was made possible through the utilization of results from AMED P-CREATE, AMED P-PROMOTE, and AMED Practical Research for Innovative Cancer Control. The projects of AMED provide research support in collaboration with universities and industry, from drug discovery target identification to clinical research.
This study is one of the world’s largest prospective studies demonstrating the clinical utility of ctDNA in colorectal cancer patients undergoing curative surgery. Measurement of ctDNA levels would lead to personalized postoperative adjuvant chemotherapy for patients undergoing curative surgery according to their risk of recurrence. To test the results of this study, a randomized phase 3 trial in ctDNA-positive patients (ALTAIR study, JapicCTI-205363) and a randomized phase 3 trial in patients who were ctDNA-negative at 4 weeks after surgery (VEGA study, jRCT1031200006) have been ongoing and results are awaited.
1. Honda K, Okusaka T, Felix K, Nakamori S, Sata N, Nagai H, et al. Altered plasma apolipoprotein modifications in patients with pancreatic cancer: protein characterization and multi-institutional validation. PLoS One. 2012;7(10):e46908.
2. Honda K, Kobayashi M, Okusaka T, Rinaudo JA, Huang Y, Marsh T, et al. Plasma biomarker for detection of early stage pancreatic cancer and risk factors for pancreatic malignancy using antibodies for apolipoprotein-AII isoforms. Sci Rep. 2015;5:15921.
3. Honda K, Srivastava S. Potential usefulness of apolipoprotein A2 isoforms for screening and risk stratification of pancreatic cancer. Biomark Med. 2016;10(11):1197-207.
4. Honda K. Risk stratification of pancreatic cancer by a blood test for apolipoprotein A2-isoforms. Cancer Biomark. 2022;33(4):503-12.
The present study was supported by funding from Toray Industries, Inc. and grants from the Japan Agency for Medical Research and Development (AMED): AMED P-CREATE [No. 21cm0106403h0006], AMED P-PROMOTE [No. 22ama221401h0001], and AMED Practical Research for Innovative Cancer Control [Nos. 19ck0106280h0003, 22ck0106661h0002].
We would like to thank Dr. Srivastava with National Cancer Institute Early Detection Research Network (NCI EDRN) for providing useful discussions on the clinical development of in vitro diagnostics.
In addition, we would like to thank Professor Kutsumi and Dr. Obata with Shiga University for supporting the approval with the regulatory science.
Professor Kazufumi Honda
Department of Bioregulation, Graduate School of Medicine,
Nippon Medical School