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  • 1
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 157-157
    Abstract: Colorectal cancer (CRC) is the third leading cause of cancer and cancer-related death. A large fraction of the CRC patients diagnosed with de novo metastatic disease do not benefit from standard of care and experience substantial side effects. Therefore, there is an urgent need for preclinical models that help predict patient response in the clinic. Patient-derived organoids (PDOs or HUB Organoids®) represent a significant breakthrough as preclinical models as they are directly established from patient tissue and faithfully recapitulate patient disease. HUB Organoid Technology can already be applied to preclinical drug screening, however, to provide direct patient benefit the turnaround time between patient diagnosis and PDO-based results must be shortened. In collaboration with Yamaha Motor, the Yamaha CELL HANDLERTM has been validated to automatically pick-and-place with high accuracy a significantly reduced number of organoids per screening plate, compared to standard procedures. In addition, an image-based readout was developed that enables a precise quantification of organoid number ensuring high assay quality. Organoid responses to chemotherapy and targeted agents were validated using this newly automated system, confirming comparable PDO-patient drug sensitivity profiles, and known drug responses based on genetic dependencies. In summary we describe the development of an automated workflow that combines patient-representative HUB Organoids and state-of-the-art robotics by Yamaha CELL HANDLER. This workflow down-scales the number of organoids needed per screening well and allows to efficiently predict patient response, thereby reducing the diagnostic turnaround time and increasing patient benefits. Citation Format: Esmee Koedoot, Inez van Weersch, Gakuro Harada, Masahiko Watanabe, Hamdy Warda, Hideaki Kyan, Yasmine Abouleila, Takahiko Kumagai, Yuichi Hikichi, René Overmeer, Jeanine Roodhart, Kiyotaka Matsuno, Carla Verissimo, Sylvia F. Boj. Patient in the lab: Down-scaling patient-derived organoid screening for diagnostic purposes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 157.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Library Location Call Number Volume/Issue/Year Availability
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  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 151-151
    Abstract: Patient-derived organoids (PDOs) are increasingly adopted in preclinical research. PDOs, or HUB Organoids®, are directly established from patient tissue, faithfully recapitulate patient disease, and effectively bridge the gap between the lab and the clinic, bringing a “patient in the lab®”. PDOs can also revolutionize clinical research because they can predict patient response to standard-of-care (SoC) compounds. However, there is an urgent need to refine the assay conditions to evaluate the activity of SoC drugs with different mechanisms of action (topoisomerase inhibitors, alkylating agents, targeted agents) and various types of molecules (small molecules, antibodies) and achieve optimal results from the PDO-based assay. Specifically, for metastatic colorectal cancer (mCRC), we have optimized the media composition required for drug screening assays to test response to SoC, such as oxaliplatin and panitumumab. Our results indicate that optimal media conditions are essential to observe an in vitro drug response in PDOs similar to the patient response in the clinic. In addition, an image-based readout was developed that enables precise quantification of organoid numbers ensuring high assay quality. Optimizing screening conditions to evaluate SoC compounds in PDOs is a required step to accelerate the implementation of the HUB Organoid Technology as a diagnostic platform to accurately predict treatment response and improve clinical outcomes for cancer patients. Citation Format: Carla S. Verissimo, Lidwien Smabers, Emerens Wensink, Esmee Koedoot, Katerina-Chara Pitsa, Mayke Doorn, Inez van Weersch, Hamdy Warda, Celia Higuera Barón, Gerben ten Hag, Robert G. Vries, Jeanine Roodhart, Sylvia F. Boj. Optimization of screening conditions using patient-derived organoids for diagnostic purposes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 151.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
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