AUTHOR=Liu Jian , Li Dan , Li Jing , Fu Wenlan , Jia Qiang , Bai Yang , Huang Axiu , Chen Fang 

TITLE=Patient-derived organoids reveal marked heterogeneity in chemosensitivity profiles of colorectal cancer and a potential association with HER2 status

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1620764

DOI=10.3389/fphar.2025.1620764

ISSN=1663-9812

ABSTRACT=This study aimed to evaluate the sensitivity and heterogeneity of standard first-line chemotherapy regimens for colorectal cancer (CRC) using patient-derived tumor organoids (PDTOs). Drug sensitivity testing in 15 CRC PDTOs revealed varying proportions of samples classified as sensitive (inhibition rate >50%) across different regimens: FOLFIRI (60%), FOLFOX (40%), CAPEOX (26.7%), and 5-Fluorouracil (26.7%). Furthermore, exploratory analysis indicated that for FOLFIRI and FOLFOX regimens, HER2(1+) status was significantly associated with lower inhibition grades compared to HER2(0) status (P < 0.05), implying a potential impact on the level of drug response. These findings demonstrate significant heterogeneity in the response of CRC PDTOs to first-line chemotherapies. Furthermore, at the organoid level, a low HER2 expression status may be associated with the heterogeneity of responses observed with specific drug regimens.