Annual Report 2021
Division of Biomarker Discovery (Kashiwa Campus)
Atsushi Ochiai, Shuichi Mitsunaga, Tomofumi Miura, Kazuyoshi Yanagihara, Yuki Iino, Yuka Nakamura, Mariko Yajima, Michiko Hamamoto, Sachiko Fukuda, Motoko Suzaki
Introduction
The Division of Biomarker Discovery is investigating tumor-induced inflammation and host reaction, which are causes of chemorefractoriness and cachexia. Our goal is the development of biomarker-driven therapy to treat not only pancreatic cancer but also cachexia symptoms.
The Team and What We Do
Our division is composed of 4 researchers and 6 research assistants. In our research work, novel therapies and biomarkers have been developed regarding interpreting and combining clinical samples and information, gene analyses, and various omics information through collaborations with many external research institutes and drug discovery companies. These results are built on the elucidation of the molecular mechanisms of the crosstalk between tumor-induced inflammation and host reaction.
Research activities
Systemic inflammatory response in pancreatic cancer patients is related to chemorefractoriness and cachexia and is caused by tumor-derived inflammation that IL-6 signaling is involved in in our research. A phase I study of gemcitabine + nab-paclitaxel in combination with anti-IL-6 receptor antibodies in patients with advanced pancreatic cancer has indicated that IL-6 inhibition is effective in such populations. In our translational research, the investigational treatment improved intratumoral drug infiltration and tumor microenvironments favorable to immune checkpoint inhibitors, which provided a POC (proof of concept) for global phase 1 trials.
GDF-15 is a cause of cachexia and anorexia. In order to explore suitable populations of pancreatic cancer patients to treat cachexia using GDF-15 inhibitors, industry-academia collaborative research was conducted and the outcomes were published. Based on this research activity, our hospital was selected as a clinical trial site for GDF-15 inhibitory therapy.
To establish a diagnostic serum microRNA test for pancreato-biliary cancer, 1374 participants were registered from 10 institutions. We constructed and verified a serum microRNA test that exceeds the diagnostic ability of the present tumor marker, CA19-9. We are working on a robust test kit that shows high reproducibility. Translational studies have shown that diagnostic microRNAs reflect the activity of tumors.
Education
One graduate student obtained a PhD.
Future Prospects
We will continue our activities to academically support IL-6 signal inhibition therapy and GDF-15 inhibition therapy, and explore new seeds through reverse translational research.
List of papers published in 2021
Journal
1. Tsuno T, Fujimiya T, Kawaguchi T, Yanaizumi R, Kojima K, Miyasato A, Azuma K, Saeki T, Mawatari H, Igarashi T, Miura T, Ogura H, Kondo J, Tanoue T, Hamada H, Oyama Y, Kotani A, Yamaguchi T, Hakamata H. Psychological barriers to the use of opioid analgesics for treating pain in patients with advanced recurrent cancer (BAROC): protocol for a multicentre cohort study. BMJ open, 12:e054914, 2022
2. Yachida S, Totoki Y, Noë M, Nakatani Y, Horie M, Kawasaki K, Nakamura H, Saito-Adachi M, Suzuki M, Takai E, Hama N, Higuchi R, Hirono S, Shiba S, Kato M, Furukawa E, Arai Y, Rokutan H, Hashimoto T, Mitsunaga S, Kanda M, Tanaka H, Takata S, Shimomura A, Oshima M, Hackeng WM, Okumura T, Okano K, Yamamoto M, Yamaue H, Morizane C, Arihiro K, Furukawa T, Sato T, Kiyono T, Brosens LAA, Wood LD, Hruban RH, Shibata T . Comprehensive Genomic Profiling of Neuroendocrine Carcinomas of the Gastrointestinal System. Cancer discovery, 12:692-711, 2022
3. Nakajima H, Harano K, Nakai T, Kusuhara S, Nakao T, Funasaka C, Kondoh C, Matsubara N, Naito Y, Hosono A, Mitsunaga S, Ishii G, Mukohara T. Impacts of clinicopathological factors on efficacy of trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer. Breast (Edinburgh, Scotland), 61:136-144, 2022
4. Usui Y, Miura T, Kawaguchi T, Kosugi K, Uehara Y, Kato M, Kosugi T, Sone M, Nakamura N, Mizushima A, Miyashita M, Morita T, Yamaguchi T, Matsumoto Y, Satomi E. Palliative care physicians' recognition of patients after immune checkpoint inhibitors and immune-related adverse events. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 30:775-784, 2022
5. Shimizu Y, Hayashi A, Maeda I, Miura T, Inoue A, Takano M, Aoyama M, Matsuoka YJ, Morita T, Kizawa Y, Tsuneto S, Shima Y, Masukawa K, Miyashita M. Changes in depressive symptoms among family caregivers of patients with cancer after bereavement and their association with resilience: A prospective cohort study. Psycho-oncology, 31:86-97, 2022
6. Yokota S, Amano K, Oyamada S, Ishiki H, Maeda I, Miura T, Hatano Y, Uneno Y, Hori T, Matsuda Y, Kohara H, Suzuki K, Morita T, Mori M, on behalf of the East-Asian collaborative cross-cultural Study to Elucidate the Dying process (EASED) investigators. Effects of artificial nutrition and hydration on survival in patients with head and neck cancer and esophageal cancer admitted to palliative care units. Clinical Nutrition Open Science, 41:33-43, 2021
7. Yokota S, Amano K, Oyamada S, Ishiki H, Maeda I, Miura T, et al. Effects of artificial nutrition and hydration on survival in patients with head and neck cancer and esophageal cancer admitted to palliative care units: Secondary analysis of a multicenter prospective cohort study. BMJ Supportive & Palliative Care, 2021
8. Amano K, Satomi E, Oyamada S, Ishiki H, Sakashita A, Miura T, Maeda I, Hatano Y, Yamauchi T, Oya K, Nakagawa J, Hiratsuka Y, Hirohashi T, Morita T, Mori M, on behalf of the East-Asian collaborative cross-cultural Study to Elucidate the Dying process(EASED) investigators. The prevalence of artificially administered nutrition and hydration in different age groups among patients with advanced cancer admitted to palliative care units. Clinical Nutrition Open Science, 40:69-78, 2021
9. Arakawa S, Amano K, Oyamada S, Maeda I, Ishiki H, Miura T, Hatano Y, Naito AS, Sato M, Ito T, Kosugi K, Miyake S, Morita T, Mori M. Effects of parenteral nutrition and hydration on survival in advanced cancer patients with malignant bowel obstruction: secondary analysis of a multicenter prospective cohort study. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 29:7541-7549, 2021
10. Miura T, Elgersma R, Okizaki A, Inoue MK, Amano K, Mori M, Chitose H, Matsumoto Y, Jager-Wittenaar H, Ottery FD . A Japanese translation, cultural adaptation, and linguistic and content validity confirmation of the Scored Patient-Generated Subjective Global Assessment. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 29:7329-7338, 2021
11. Miura T, Okizaki A, Hasuo H, Satomi E, Tagami K, Imai K, Kojima T, Satake H, Ishiki H, Inoue A, Yamaguchi T. Dexamethasone 8 mg for Cancer-Related Fatigue in Inpatients with Advanced Cancer Undergoing Palliative Care: A Multicenter Phase II Trial. Palliative medicine reports, 2:316-323, 2021
12. Sasaki M, Ueno H, Mitsunaga S, Ohba A, Hosoi H, Kobayashi S, Ueno M, Terazawa T, Goto M, Inoue D, Namiki S, Sakamoto Y, Kondo S, Morizane C, Ikeda M, Okusaka T. A phase II study of FOLFIRINOX with primary prophylactic pegfilgrastim for chemotherapy-naïve Japanese patients with metastatic pancreatic cancer. International journal of clinical oncology, 26:2065-2072, 2021
13. Amano K, Satomi E, Oyamada S, Ishiki H, Sakashita A, Miura T, et al. The prevalence and use of artificial nutrition and hydration in different age groups among patients with advanced cancer admitted to palliative care units: Secondary analysis of a multicenter prospective cohort study . BMJ Supportive & Palliative Care, 2021
14. Suzuki H, Mitsunaga S, Ikeda M, Aoyama T, Yoshizawa K, Yoshimatsu H, Kawai N, Masuda M, Miura T, Ochiai A. Clinical and Tumor Characteristics of Patients with High Serum Levels of Growth Differentiation Factor 15 in Advanced Pancreatic Cancer. Cancers, 13:2021
15. Imaoka H, Sasaki M, Hashimoto Y, Watanabe K, Miyazawa S, Shibuki T, Mitsunaga S, Ikeda M. Impact of Endoscopic Ultrasound-Guided Tissue Acquisition on Decision-Making in Precision Medicine for Pancreatic Cancer: Beyond Diagnosis. Diagnostics (Basel, Switzerland), 11:2021
16. Ishii T, Suzuki A, Kuwata T, Hisamitsu S, Hashimoto H, Ohara Y, Yanagihara K, Mitsunaga S, Yoshino T, Kinoshita T, Ochiai A, Shitara K, Ishii G. Drug-exposed cancer-associated fibroblasts facilitate gastric cancer cell progression following chemotherapy. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 24:810-822, 2021
17. Amano K, Ishiki H, Miura T, Maeda I, Hatano Y, Oyamada S, Yokomichi N, Tagami K, Odagiri T, Ito T, Baba M, Morita T, Mori M. C-Reactive Protein and Its Relationship with Pain in Patients with Advanced Cancer Cachexia: Secondary Cross-Sectional Analysis of a Multicenter Prospective Cohort Study. Palliative medicine reports, 2:122-131, 2021
18. Kosugi K, Nishiguchi Y, Miura T, Fujisawa D, Kawaguchi T, Izumi K, Takehana J, Uehara Y, Usui Y, Terada T, Inoue Y, Natsume M, Yajima MY, Watanabe YS, Okizaki A, Matsushima E, Matsumoto Y. Association Between Loneliness and the Frequency of Using Online Peer Support Groups Among Cancer Patients With Minor Children: A Cross-Sectional Web-Based Study. Journal of pain and symptom management, 61:955-962, 2021
19. Ikeda M, Okusaka T, Ohno I, Mitsunaga S, Kondo S, Ueno H, Morizane C, Gemmoto K, Suna H, Ushida Y, Furuse J. Phase I studies of peptide vaccine cocktails derived from GPC3, WDRPUH and NEIL3 for advanced hepatocellular carcinoma. Immunotherapy, 13:371-385, 2021