The Journal of Practical Medicine >

2025 , Vol. 41 >Issue 18: 2786 - 2795

DOI: https://doi.org/10.3969/j.issn.1006-5725.2025.18.002

Feature Reports：Breast carcinoma

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

  • Yingchao WU ,
  • Liushan CHEN ,
  • Yuqi LIANG ,
  • Jieting CHEN ,
  • Junfeng HUANG ,
  • Qian ZUO ,
  • Qianjun CHEN
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  • 1.Chinese Medicine Guangdong Laboratory，Hengqin 519031，Guangdong，China
    2.The Second Clinical Medical College of Guangzhou University of Chinese Medicine，Guangzhou 510405，Guangdong，China
    3.State Key Laboratory of Traditional Chinese Medicine Syndrome，the Second Affiliated Hospital of Guangzhou University of Chinese Medicine，Guangzhou 510120，Guangdong，China
    4.Department of Breast，Guangdong Provincial Hospital of Chinese Medicine，Guangzhou 510120，Guangdong，China
    5.Guangdong Academy of Traditional Chinese Medicine，Guangzhou 510120，Guangdong，China

Received date: 2025-06-17

  Online published: 2025-09-25

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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 significantly 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.

Key words： breast cancer; HR+/HER2-low; ET+CDK4/6 inhibitor; organoid; tyrosine kinase inhibitor

Cite this article

Yingchao WU , Liushan CHEN , Yuqi LIANG , Jieting CHEN , Junfeng HUANG , Qian ZUO , Qianjun CHEN . 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[J]. The Journal of Practical Medicine, 2025 , 41(18) : 2786 -2795 . DOI: 10.3969/j.issn.1006-5725.2025.18.002

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