Development of an organoid-based pan-TKI precision screening platform to enhance therapeutic efficacy of ET+CDK4/6 inhibitors in HR+/HER2-low breast cancer
10.3969/j.issn.1006-5725.2025.18.002
- VernacularTitle:基于类器官构建泛TKI提高ET+CDK4/6抑制剂治疗HR+/HER2-low乳腺癌疗效的筛选工具
- Author:
Yingchao WU
1
;
Liushan CHEN
;
Yuqi LIANG
;
Jieting CHEN
;
Junfeng HUANG
;
Qian ZUO
;
Qianjun CHEN
Author Information
1. 中医药广东省实验室(广东横琴 519031);广州中医药大学第二临床医学院(广东 广州 510405);广州中医药大学第二附属医院中医证候全国重点实验室(广东 广州 510120);广东省中医院乳腺科(广东 广州 510120);广东省中医药科学院(广东 广州 510120)
- Publication Type:Journal Article
- Keywords:
breast cancer;
HR+/HER2-low;
ET+CDK4/6 inhibitor;
organoid;
tyrosine kinase in-hibitor
- From:
The Journal of Practical Medicine
2025;41(18):2786-2795
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the underlying mechanisms contributing to the limited therapeutic efficacy of endocrine therapy combined with CDK4/6 inhibitors in HR+/HER2-low breast cancer,and to develop a breast cancer organoid model as a tool for the precise identification of HR+/HER2-low patients who are responsive to pan-TKI treatment.Methods Transcriptomics was employed to identify differentially expressed genes in HR+/HER2-0 and HR+/HER2-low breast cancer samples and to perform functional enrichment analysis.Tumor organoid models were established using breast cancer tissues obtained from clinical sources,and the differential sensitivity of these samples to therapeutic agents was assessed using Calcein-AM/PI cell viability staining and EdU-based cell proliferation assays.Results The results of transcriptomic enrichment analysis indicated that EGFR was signifi-cantly activated in HR+/HER2-low breast cancer and exhibited characteristics of resistance to TKIs.Breast cancer organoids were successfully established.Drug sensitivity testing revealed that the therapeutic efficacy of ET combined with CDK4/6 inhibitors was suboptimal in certain cases of HR+/HER2-low breast cancer,while the addition of TKIs effectively restored sensitivity to the ET+CDK4/6 inhibitor regimen(P<0.05).Conclusions TKI can restore the reduced sensitivity of HR+/HER2-low breast cancer to endocrine therapy combined with CDK4/6 inhibitors.Breast cancer organoids hold promise as screening tools for assessing drug sensitivity in clinical settings for patients with HR+/HER2-low breast cancer.
