한빛사논문
- 조회594
YongHwan Kim,1,13 Hyein Ju,1,13 Seung-Yeon Yoo,2,13 Jinahn Jeong,3 Jinbeom Heo,1 Seungun Lee,1 Ja-Min Park,3 Sun Young Yoon,3 Se Un Jeong,4 Jinyoung Lee,5 HongDuck Yun,1 Chae-Min Ryu,6 Jinah Lee,1 Yun Ji Nam,1 Hyungu Kwon,1 Jaekyoung Son,5 Gowun Jeong,7 Ji-Hye Oh,3 Chang Ohk Sung,3 Eui Man Jeong,8 Jaehoon An,9,10 Sungho Won,9,10 Bumsik Hong,11 Jae Lyun Lee,12,* Yong Mee Cho,3,* and Dong-Myung Shin1,14,*
1Department of Cell and Genetic Engineering, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
2Pathology Center, Seegene Medical Foundation, Seoul 04805, Korea
3Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
4Department of Pathology, Ewha Womans University College of Medicine, Ewha Womans University Mokdong Hospital, Seoul 07985, Korea
5Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
6Center for Cell Therapy, Asan Medical Center, Seoul 05505, Korea
7AI Recommendation, T3K, SK Telecom, Seoul 04539, Korea
8College of Pharmacy, Jeju National University, Jeju 63243, Korea
9Department of Public Health Sciences, Seoul National University, Seoul 08826, Korea
10RexSoft, Inc., Seoul 08826, Korea
11Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
12Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
13These authors contributed equally
14Lead contact
*Corresponding authors: correspondence to Jae Lyun Lee, Yong Mee Cho or Dong-Myung Shin
Abstract
Radical cystectomy with preoperative cisplatin-based neoadjuvant chemotherapy (NAC) is the standard care for muscle-invasive bladder cancers (MIBCs). However, the complete response rate to this modality remains relatively low, and current clinicopathologic and molecular classifications are inadequate to predict NAC response in patients with MIBC. Here, we demonstrate that dysregulation of the glutathione (GSH) pathway is fundamental for MIBC NAC resistance. Comprehensive analysis of the multicohort transcriptomes reveals that GSH metabolism and immune-response genes are enriched in NAC-resistant and NAC-sensitive MIBCs, respectively. A machine-learning-based tumor/stroma classifier is applied for high-throughput digitalized immunohistochemistry analysis, finding that GSH dynamics proteins, including glutaminase-1, are associated with NAC resistance. GSH dynamics is activated in cisplatin-resistant MIBC cells, and combination treatment with a GSH dynamics modulator and cisplatin significantly suppresses tumor growth in an orthotopic xenograft animal model. Collectively, these findings demonstrate the predictive and therapeutic values of GSH dynamics in determining the NAC response in MIBCs.
논문정보
- Research article
- 2023년 10월 (BRIC 등록일 2023-10-06)
- 국내 연구진
- 의약학 > 분자세포의학
관련 웨비나
![Glutathione dynamics 조절을 통한 방광암 신보조 화학요법 반응의 잠재적 예측과 치료 [Cell Rep. Med]](/upload/board/files/onseminar/thumb/thumb_0000632.png)
학술웨비나
Glutathione dynamics 조절을 통한 방광암 신보조 화학요법 반응의 잠재적 예측과 치료 [Cell Rep. Med] 방광암은 암세포가 방광 근육을 침범했는지 여부에 따라 비근침윤성 방광암(Non–muscle Invasive Bladder Cancer, NMIBC)과 근침윤성 방광암(Muscle Invasive Bladder Cancer, MIBC)로 나뉩니다. 특히, 근침윤성 방광암은 근치적 방광 절제술과 수술 전 시스플라틴 기반 신보조 화학요법(Neoadjuvant chemotherapy, NAC)가 표준 치료방법인데, 이러한 치료의 반응을 사전에 예측하기 어려운 난치성 암 종류로 알려져 있습니다. 이 연구에서는 근침윤성 방광암 환자를 연구하여, glutaminase-1(GLS)와 같은 글루타치온(Glutathione, GSH) 조절 인자들이 방광암 치료의 반응성을 조절하고 예측하는데 중요한 역할을 한다는 결과를 제시합니다.- 김용환(울산대학교 의과대학, 서울아산병원)
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