Patient-derived organoids as a platform for drug screening in metastatic colorectal cancer

Xingfeng He; Yan Jiang; Long Zhang; Yaqi Li; Xiang Hu; Guoqiang Hua; Sanjun Cai; Shaobo Mo; Junjie Peng

doi:10.3389/fbioe.2023.1190637

Patient-derived organoids as a platform for drug screening in metastatic colorectal cancer

Front Bioeng Biotechnol. 2023 May 22:11:1190637. doi: 10.3389/fbioe.2023.1190637. eCollection 2023.

Authors

Xingfeng He^{1

2}, Yan Jiang³, Long Zhang^{1

2}, Yaqi Li^{1

2}, Xiang Hu^{1

2}, Guoqiang Hua^{2

4}, Sanjun Cai^{1

2}, Shaobo Mo^{1

2}, Junjie Peng^{1

2}

Affiliations

¹ Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
² Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
³ Department of Nursing Administration, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
⁴ Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Abstract

Introduction: Most advanced colorectal cancers are aggressive, and there is a lack of effective methods for selecting appropriate anticancer regimens. Patient-derived organoids (PDOs) have emerged as preclinical platforms for modeling clinical responses to cancer therapy. Methods: In this study, we successfully constructed a living biobank with 42 organoids derived from primary and metastatic lesions of metastatic colorectal cancer patients. Tumor tissue was obtained from patients undergoing surgical resection of the primary or metastatic lesion and then used to establish PDOs. Immunohistochemistry (IHC) and drug sensitivity assays were performed to analyze the properties of these organoids. Results: The mCRC organoids were successfully established with an 80% success rate. The PDOs maintained the genetic and phenotypic heterogeneity of their parental tumors. The IC50 values of5-fluorouracil (5-FU), oxaliplatin, and irinotecan (CPT11) were determined for mCRC organoids using drug sensitivity assays. The in vitro chemosensitivity data revealed the potential value of PDOs for clinical applications in predicting chemotherapy response and clinical outcomes in mCRC patients. Discussion: In summary, the PDO model is an effective platform for in vitro assessment of patient-specific drug sensitivity, which can guide personalized treatment decisions for patients with end-stage CRC.

Keywords: drug screening; metastatic colorectal cancer; patient-derived organoids; personalized therapy; preclinical model.

Grants and funding

National Natural Science Foundation of China; Grant numbers 82203215 (to SM), 82173461 (to GH), U1932145 (to JP), 82002946 (to YL); Fudan University Shanghai Cancer Center Basic and Clinical Translational Research Seed Foundation; Grant Number: YJZZ201802 (to SC); Science and Technology Commission of Shanghai Municipality; Grant Number: 18401933402 (to JP); Shanghai Sailing Program; Grant Number: 22YF1408800 (to SM).