Editors' ChoiceCancer

Rapid drug screen using 3D tumor organoids

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Science Translational Medicine  10 Jan 2018:
Vol. 10, Issue 423, eaar7507
DOI: 10.1126/scitranslmed.aar7507


Breast cancer organoids enable high-throughput functional drug screens to potentially guide individualized therapy.

Breast cancer is the most common cancer and the second leading cause of cancer death in women worldwide. Recent advances in phenotyping technologies have revealed high inter- and intratumor heterogeneity in breast cancer, which affect disease progression and treatment options. However, turning this knowledge into personalized treatment remains a challenge. This is in part due to a lack of an in vitro platform that can capture the pathological properties of patient-specific cancers. The most commonly used preclinical models are cell lines and patient-derived xenografts. Establishing these models, however, takes months of labor-intensive process, making it impossible to be used for testing personalized therapy.

In a recent study, Sachs et al. developed a robust protocol that enables the production of three-dimensional epithelial organoids using tumor cells from patient breast biopsy samples. The authors successfully established 95 organoids from 155 tumors. Histological characterization of the organoids matched the original histological cancer types. Immunohistochemistry analysis confirmed that the organoids retain expression of the prevalent breast cancer biomarkers, such as estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). In addition, gene expression analysis showed that the organoids display representative gene expression profiles of breast cancer subtypes. These results suggest that the organoids recapitulate key histological and genetic features of breast cancer.

To test if they allow physiologically relevant drug screens, the researchers exposed the organoids to drugs targeting the HER signaling pathway. Most of the HER2-positive organoids responded to the drugs, but a few patient-derived organoids violated this trend, highlighting the value of in vitro drug testing using this approach. To directly correlate in vitro drug response to patient responses, they generated 12 organoids from needle biopsies of 13 patients with metastatic breast cancer. These organoids’ responses to tamoxifen matched that of the respective patients, indicating the potential use of the organoids as tools for predicting therapeutic responses and screening effective treatments for individual patients.

This study demonstrates the potential of breast cancer organoids as a functional high-throughput drug screen platform for personalized medicine. These organoids could test individual treatment options for patients without the specific knowledge of the underlying cellular and molecular mechanisms of patient breast cancer subtypes. The authors made this representative, well-characterized, growing library of breast cancer organoids available for the research community to advance cancer research and drug development.

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