Organoid models of drug resistant gastric adenosquamous carcinoma: Recapitulating tumor features and refining precision treatment

Kuan Li; Wenchao Li; Shuying Fu; Chen Wang; Kexin Wang; Huan Yang; Yumei Xian; Tengfei Hao; Shiwei Zhang; Tianshun Gao; Jie Zhou; Jia Li; Changhua Zhang; Wei Chen; Leli Zeng; Yulong He

doi:10.1016/j.drup.2025.101201

Organoid models of drug resistant gastric adenosquamous carcinoma: Recapitulating tumor features and refining precision treatment

Drug Resist Updat. 2025 Jan 7:79:101201. doi: 10.1016/j.drup.2025.101201. Online ahead of print.

Authors

Kuan Li¹, Wenchao Li², Shuying Fu³, Chen Wang¹, Kexin Wang³, Huan Yang⁴, Yumei Xian³, Tengfei Hao¹, Shiwei Zhang¹, Tianshun Gao³, Jie Zhou⁵, Jia Li⁶, Changhua Zhang⁷, Wei Chen⁸, Leli Zeng⁹, Yulong He¹⁰

Affiliations

¹ Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong 518107, China.
² Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong 518107, China; The Department of Thyroid and Breast Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
³ The Biobank, Scientific Research Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518107, China.
⁴ Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun-Yat-sen University, Zhongshan Second Road 58, Guangzhou 510080, China.
⁵ State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong. Electronic address: jiezhou@hku.hk.
⁶ Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong 518107, China; The Biobank, Scientific Research Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518107, China.
⁷ Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong 518107, China; The Biobank, Scientific Research Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518107, China. Electronic address: zhchangh@mail.sysu.edu.cn.
⁸ Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong 518107, China; The Biobank, Scientific Research Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518107, China. Electronic address: chenw296@mail.sysu.edu.cn.
⁹ Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong 518107, China; The Biobank, Scientific Research Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518107, China. Electronic address: zenglli6@mail.sysu.edu.cn.
¹⁰ Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong 518107, China; The Biobank, Scientific Research Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518107, China. Electronic address: heyulong@mail.sysu.edu.cn.

PMID: 39793300
DOI: 10.1016/j.drup.2025.101201

Abstract

Organoids were successfully established from primary tumor and its metastatic lymph nodes of a patient. These organoids faithfully replicated tumor pathology and genetic characteristics. Organoid-based drug screening was conducted, which revealed significant difference in sensitivity to drugs between organoids dervived from primary tumor versus metastatic lymph nodes. The results guided clinical decisions for personalized treatment for the patient. This approach provides an insightful strategy for advancing treatment for gastric cancer.

Keywords: Drug resistance; Drug sensitivity test; Gastric adenosquamous carcinoma; Individualized therapy; Organoid.