Details

Autor(en) / Beteiligte

• Wu, Huizi
• Wang, Weiwei
• Zhang, Yinbin
• Chen, Yinxi
• Shan, Changyou
• Li, Jia
• Jia, Yiwei
• Li, Chaofan
• Du, Chong
• Cai, Yifan
• Zhang, Yu
• Zhang, Shuqun
• Wu, Fei

Titel

Establishment of patient‐derived organoids for guiding personalized therapies in breast cancer patients

Ist Teil von

• International journal of cancer, 2024-07, Vol.155 (2), p.324-338

Ort / Verlag

Hoboken, USA: John Wiley & Sons, Inc

Erscheinungsjahr

2024

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Breast cancer has become the most commonly diagnosed cancer. The intra‐ and interpatient heterogeneity induced a considerable variation in treatment efficacy. There is an urgent requirement for preclinical models to anticipate the effectiveness of individualized drug responses. Patient‐derived organoids (PDOs) can accurately recapitulate the architecture and biological characteristics of the origin tumor, making them a promising model that can overtake many limitations of cell lines and PDXs. However, it is still unclear whether PDOs‐based drug testing can benefit breast cancer patients, particularly those with tumor recurrence or treatment resistance. Fresh tumor samples were surgically resected for organoid culture. Primary tumor samples and PDOs were subsequently subjected to H&E staining, immunohistochemical (IHC) analysis, and whole‐exome sequencing (WES) to make comparisons. Drug sensitivity tests were performed to evaluate the feasibility of this model for predicting patient drug response in clinical practice. We established 75 patient‐derived breast cancer organoid models. The results of H&E staining, IHC, and WES revealed that PDOs inherited the histologic and genetic characteristics of their parental tumor tissues. The PDOs successfully predicted the patient's drug response, and most cases exhibited consistency between PDOs' drug susceptibility test results and the clinical response of the matched patient. We conclude that the breast cancer organoids platform can be a potential preclinical tool used for the selection of effective drugs and guided personalized therapies for patients with advanced breast cancer. What's new? Heterogeneity in breast cancer contributes to variations in treatment effectiveness. Patient‐derived organoids (PDOs) have emerged as promising models to predict individualized drug responses, though their applicability to breast cancer remains largely unexplored. Here, the authors established a biobank of breast cancer PDOs to evaluate their feasibility in predicting patient drug response. Experiments demonstrate that the PDOs accurately inherit the histologic and genetic characteristics of the breast tumors from which they are derived. Moreover, drug susceptibility in PDOs corresponded to clinical responses in matched patients. The findings highlight the potential utility of PDOs in guiding personalized therapy for breast cancer patients.