Annual Report 2022
Division of Biomarker Discovery (KASHIWA CAMPUS)
Shuichi Mitsunaga, Tomofumi Miura, Hidetaka Suzuki, Mariko Yajima, Michiko Hamamoto, Reiko Nakamura
Introduction
The Division of Biomarker Discovery is investigating tumor-induced inflammation and host reactions, which are the causes of chemorefractory and cachexia. Our goal is to develop a biomarker-driven therapy to treat both pancreatic cancer and cachexia symptoms.
The Team and What We Do
Our division is composed of 3 researchers and 3 research assistants. Through our research, novel therapies and biomarkers have been developed on the interpretation of combining clinical samples and information, gene analyses, and various Omics information through collaborations with many external research institutes and drug discovery companies, which are built based on the elucidation of the molecular mechanism of the crosstalk between tumor-induced inflammation and host reaction.
Research Activities
The systemic inflammatory response in patients with pancreatic cancer is associated with chemo-refractory and cachexia and is caused by tumor-derived inflammation in which IL-6 signaling is involved in our research. We have established a murine nerve-invasion model using human pancreatic cancer cells (N-inv model) to represent systemic inflammation and cachexia. Analysis of the N-inv model revealed that IL-6 signaling activity promoted nerve invasion of pancreatic cancer cells. Inhibition of IL-6 signaling was beneficial for the suppression of nerve invasion. These data encouraged us to develop IL-6 inhibitory therapy for patients with pancreatic cancer, which were published in a peer-reviewed journal article.
A translational collaborative research was conducted using clinical samples and data from a phase I study of gemcitabine + nab-paclitaxel in combination with anti-IL-6 receptor antibody in patients with advanced pancreatic cancer. This research provided evidence that peripheral CD8+ effector memory T cells predicted clinical benefits, such as tumor reduction and non-cachexia, with chemotherapy plus IL-6 inhibition. These data were patented in collaboration with a pharmaceutical company.
We are working on a serum microRNA test that exceeds the diagnostic ability of the present tumor marker, CA19-9, using clinical samples and data from 1487 participants in 10 institutions. Using these maneuvers, we constructed a serum microRNA signature to predict systemic deterioration in various cancer patients. These data were published in a peer-reviewed journal article.
Future Prospects
We will continue activities to academically support IL-6 signal inhibition therapy and diagnostic serum microRNA tests, and explore new seeds through reverse translational research.
List of papers published in 2022
Journal
1. Habu T, Kumanishi R, Ogata T, Fujisawa T, Mishima S, Kotani D, Kadowaki S, Nakamura M, Hojo H, Fujiwara H, Kumagai S, Koyama S, Fujita T, Kinoshita T, Nishikawa H, Yano T, Tajika M, Muro K, Mitsunaga S, Kojima T, Bando H. Complete response to definitive chemoradiotherapy in unresectable locally advanced esophageal squamous cell carcinoma. Esophagus, 20:533-540, 2023
2. Sato K, Fujita T, Matsuzaki H, Takeshita N, Fujiwara H, Mitsunaga S, Kojima T, Mori K, Daiko H. Real-time detection of the recurrent laryngeal nerve in thoracoscopic esophagectomy using artificial intelligence. Surgical endoscopy, 36:5531-5539, 2022
3. Miura T, Mitsunaga S, Matsuzaki J, Takizawa S, Kato K, Ochiai A, Ochiya T. Serum microRNAs as new criteria for referral to early palliative care services in treatment-naïve advanced cancer patients. Oncotarget, 13:1341-1349, 2022
4. Sato K, Fujita T, Matsuzaki H, Takeshita N, Fujiwara H, Mitsunaga S, Kojima T, Mori K, Daiko H. Correction to: Real-time detection of the recurrent laryngeal nerve in thoracoscopic esophagectomy using artificial intelligence. Surgical endoscopy, 36:9483, 2022
5. Sasaki K, Ito M, Kobayashi S, Kitaguchi D, Matsuzaki H, Kudo M, Hasegawa H, Takeshita N, Sugimoto M, Mitsunaga S, Gotohda N. Automated surgical workflow identification by artificial intelligence in laparoscopic hepatectomy: Experimental research. International journal of surgery (London, England), 105:106856, 2022
6. 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
7. 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
8. Suzuki H, Mitsunaga S, Ikeda M, Aoyama T, Yoshizawa K, Yamaguchi M, Suzuki M, Narita M, Kawasaki T, Ochiai A. Interleukin 6/gp130 axis promotes neural invasion in pancreatic cancer. Cancer medicine, 11:5001-5012, 2022
9. Irisawa A, Takeno M, Watanabe K, Takahashi H, Mitsunaga S, Ikeda M. Incidence of and risk factors for severe neutropenia during treatment with the modified FOLFIRINOX therapy in patients with advanced pancreatic cancer. Scientific reports, 12:15574, 2022