Patient-derived micro-organospheres enable clinical precision oncology

Ding, Shengli; Hsu, Christine D.; Wang, Zhaohui; Natesh, Naveen; Millen, Rosemary; Negrete, Marcos; Giroux, Nicholas; Rivera, Grecia O.; Dohlman, Anders B.; Bose, Shree; Rotstein, Tomer; Spiller, Kassandra; Yeung, Athena; Sun, Zhiguo; Jiang, Chongming; Rui, Xiaoting; Wilkin, Benjamin; Randon, Peggy M.; Williamson, Ian; Nelson, Daniel; Delubac, Daniel; Oh, Soram; Rupprecht, Gabrielle; Isaacs, James; Jia, Jingquan; Chen, Chao; Shen, John Paul; Kopetz, Scott; McCall, Shannon J.; Smith, Amber Rae; Gjorevski, Nikolche; Walz, Antje-Christine; Antonia, Scott; Marrer-Berger, Estelle; Clevers, Hans; Hsu, David S.; Shen, Xiling

doi:10.1016/j.stem.2022.04.006

Cited by 83 publications

(70 citation statements)

References 52 publications

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“…The success of precision oncology relies on models that recapitulate the tumor microenvironment and predicate drug response for individual patients [43]. Organoids are a reliable in vitro model with high similarity to tissues, and offer an unprecedented opportunity for precise oncology.…”

Section: Discussionmentioning

confidence: 99%

Establishment of organoid models based on a nested array chip for fast and reproducible drug testing in colorectal cancer therapy

et al. 2022

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The conventional microwell-based platform for construction of organoid models exhibits limitations in precision oncology applications because of low-speed growth and high variability. Here, we established organoid models on a nested array chip for fast and reproducible drug testing using 50% matrigel. First, we constructed mouse small intestinal and colonic organoid models. Compared with the conventional microwell-based platform, the mouse organoids on the chip showed accelerated growth and improved reproducibility due to the nested design of the chip. The design of the chip provides miniaturized and uniform shaping of the matrigel that allows the organoid to grow in a concentrated and controlled manner. Next, a patient-derived organoid (PDO) model from colorectal cancer tissues was successfully generated and characterized on the chip. Finally, the PDO models on the chip, from three patients, were implemented for high-throughput drug screening using nine treatment regimens. The drug sensitivity testing on the PDO models showed good quality control with a coefficient of variation under 10% and a Z' factor of more than 0.7. More importantly, the drug responses on the chip recapitulate the heterogeneous response of individual patients, as well as showing a potential correlation with clinical outcomes. Therefore, the organoid model coupled with the nested array chip platform provides a fast and reproducible means for predicting drug responses to accelerate precise oncology.

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Section: Discussionmentioning

confidence: 99%

Establishment of organoid models based on a nested array chip for fast and reproducible drug testing in colorectal cancer therapy

et al. 2022

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“…MOSs, which retain original tissue composition and cellular properties, do not require multiple passaging and can be screened immediately upon establishment. Our recent published study demonstrated that a rapid MOS drug assay based on an 18G biopsy reliably predicted the clinical responses of patients with CRC liver metastasis to chemotherapy within 14 days ( Ding et al., 2022 ). Furthermore, extrapolating to other types of assays for a variety of indications, MOSs allow uniform nutrient accessibility, direct viral infection, and efficient T cell infiltration due to small size and large surface-to-volume ratio.…”

Section: Discussionmentioning

confidence: 99%

Rapid tissue prototyping with micro-organospheres

et al. 2022

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“…A growing body of literature indicates that chemotherapy responses found in oncologic practice are closely matched by drug testing performed in parallel on patient‐derived organoids 54–56 . A recently reported technique for generation of micro‐organospheres from patient tissue biopsies allows assessment of drug response within 14 days and can reliably predict outcomes of front‐line chemotherapy 57 . This exciting technology has the potential to transform clinical trial design and precision medicine in gastrointestinal oncology.…”

Section: Biology Of Colorectal Neoplasia and In Vitro Modelingmentioning

confidence: 99%

“…[54][55][56] A recently reported technique for generation of micro-organospheres from patient tissue biopsies allows assessment of drug response within 14 days and can reliably predict outcomes of front-line chemotherapy. 57 This exciting technology has the potential to transform clinical trial design and precision medicine in gastrointestinal oncology.…”

Section: Biology Of Colorectal Neoplasia and In Vitro Modelingmentioning

confidence: 99%

Colorectal cancer

Paty

Garcia‐Aguilar

2022

Journal of Surgical Oncology

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Although surgery is the established standard and mainstay for treatment of colorectal cancer, advances in technology and clinical trials over the past 50 years have dramatically expanded and improved the detection, staging, treatment, and understanding of this disease. This review highlights contributions by surgeons, oncologists, gastroenterologists, engineers, and scientists to increase postsurgical recurrence-free survival, reduce the time and toxicity of treatment, and improve the quality of life for patients over the past half-century.

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Patient-derived micro-organospheres enable clinical precision oncology

Cited by 83 publications

References 52 publications

Establishment of organoid models based on a nested array chip for fast and reproducible drug testing in colorectal cancer therapy

Establishment of organoid models based on a nested array chip for fast and reproducible drug testing in colorectal cancer therapy

Rapid tissue prototyping with micro-organospheres

Colorectal cancer

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