Gastric cancer patient-derived organoids model for the therapeutic drug screening

• Published in: Biochimica et biophysica acta. General subjects Vol. 1868; no. 4; p. 130566
• Main Authors: Xu, Jiao, Gong, Jin, Li, Mengyang, Kang, Ye, Ma, Jinrong, Wang, Xi, Liang, Xiao, Qi, Xin, Yu, Bixin, Yang, Jin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2024
• Subjects: Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; COTI-2; Drug Evaluation, Preclinical; Early Detection of Cancer; Gastric cancer; Humans; Napabucasin; Organoids; Organoids biobank; Personalized medicine; Stomach Neoplasms - drug therapy; Stomach Neoplasms - pathology; Organoids biobank; COTI-2; Napabucasin; Personalized medicine; Gastric cancer
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2024.130566

Gastric cancer (GC) is a highly heterogeneous disease featuring many various histological and molecular subtypes. Therefore, it is imperative to have well-characterized in vitro models for personalized treatment development. Gastric cancer patient-derived organoids (PDOs), re-capitulating in vivo conditions, exhibit high clinical efficacy in predicting drug sensitivity to facilitate the development of cancer precision medicine. PDOs were established from surgically resected GC tumor tissues. Histological and molecular characterization of PDOs and primary tissues were performed via IHC and sequencing analysis. We also conducted drug sensitivity tests using PDO cultures with five chemotherapeutic drugs and twenty-two targeted drugs. We have successfully constructed a PDOs biobank that included EBV+, intestinal/CIN, diffuse/GS, mixed and Her2+ GC subtypes, and these PDOs captured the pathological and genetic characteristics of corresponding tumors and exhibited different sensitivities to the tested agents. In a clinical case study, we performed an additional drug sensitivity test for a patient who reached an advanced progressive stage after surgery. We discovered that the combination of napabucasin and COTI-2 exhibited a stronger synergistic effect than either drug alone. PDOs maintained the histological and genetic characteristics of original cancer tissues. PDOs biobank opens up new perspectives for studying cancer cell biology and personalized medicine as a preclinical study platform. •Living biobank encompassed 18 normal and 21 gastric cancer organoids.•Established organoids biobank included most of the known subtypes of gastric cancer.•High-throughput screening revealed potential targeted drugs for personalized medicine.•Napabucasin combined with COTI-2 indicated a potential therapy strategy for advanced progressive patients of gastric cancer.