한빛사논문
- 조회371
엠비디
Sang-Yun Lee1,2†, Hyeong Jun Cho3†, Jimin Choi2†, Bosung Ku2, Seok Whan Moon4, Mi Hyoung Moon4, Kyung Soo Kim4, Kwanyong Hyun4, Tae-Jung Kim5, Yeoun Eun Sung5, Yongki Hwang3, Eunyoung Lee3, Dong Hyuck Ahn3, Joon Young Choi6, Jeong Uk Lim7, Chan Kwon Park7, Sung Won Kim8,9, Seung Joon Kim3,10, In-Seong Koo1, Woo Seok Jung1, Sang-Hyun Lee2*, Chang Dong Yeo11* and Dong Woo Lee1*
1Department of Biomedical Engineering, Gachon University, Seongnam 13120, Republic of Korea
2Central R & D Center, Medical & Bio Decision (MBD) Co., Ltd, Suwon 16229, Republic of Korea
3Division of Pulmonology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
4Department of Thoracic and Cardiovascular Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
5Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
6Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
7Division of Pulmonary, Critical Care and Allergy, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
8Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
9Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
10Postech-Catholic Biomedical Engineering Institute, College of Medicine, The Catholic University of Korea, Songeui Multiplex Hall, Seoul, Republic of Korea
11Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
†Sang-Yun Lee, Hyeong Jun Cho and Jimin Choi contributed equally.
*Correspondence: Sang-Hyun Lee, Chang Dong Yeo, Dong Woo Lee
Abstract
Background
Recently, cancer organoid-based drug sensitivity tests have been studied to predict patient responses to anticancer drugs. The area under curve (AUC) or IC50 value of the dose-response curve (DRC) is used to differentiate between sensitive and resistant patient‘s groups. This study proposes a multi-parameter analysis method (cancer organoid-based diagnosis reactivity prediction, CODRP) that considers the cancer stage and cancer cell growth rate, which represent the severity of cancer patients, in the sensitivity test.
Methods
On the CODRP platform, patient-derived organoids (PDOs) that recapitulate patients with lung cancer were implemented by applying a mechanical dissociation method capable of high yields and proliferation rates. A disposable nozzle-type cell spotter with efficient high-throughput screening (HTS) has also been developed to dispense a very small number of cells due to limited patient cells. A drug sensitivity test was performed using PDO from the patient tissue and the primary cancer characteristics of PDOs were confirmed by pathological comparision with tissue slides.
Results
The conventional index of drug sensitivity is the AUC of the DRC. In this study, the CODRP index for drug sensitivity test was proposed through multi-parameter analyses considering cancer cell proliferation rate, the cancer diagnosis stage, and AUC values. We tested PDOs from eight patients with lung cancer to verify the CODRP index. According to the anaplastic lymphoma kinase (ALK) rearrangement status, the conventional AUC index for the three ALK-targeted drugs (crizotinib, alectinib, and brigatinib) did not classify into sensitive and resistant groups. The proposed CODRP index-based drug sensitivity test classified ALK-targeted drug responses according to ALK rearrangement status and was verified to be consistent with the clinical drug treatment response.
Conclusions
Therefore, the PDO-based HTS and CODRP index drug sensitivity tests described in this paper may be useful for predicting and analyzing promising anticancer drug efficacy for patients with lung cancer and can be applied to a precision medicine platform.
논문정보
- Research article
- 2023년 11월 (BRIC 등록일 2023-12-04)
- 국내 연구진
- 바이오·의료융합 > 의료기기
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
관련분야 논문보기
