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  • 1
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 4112-4112
    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 the standard of care but still experience substantial side effects. Therefore, there is the urgency for a new model to predict clinical response. Adult epithelial stem cell (ASC) -derived organoids are proving to be a major breakthrough in pre-clinical models. ASC-derived organoids can be developed from healthy as well as diseased tissue, including cancer lesions and therefore are often referred to as patient-derived organoids (PDOs or HUB Organoids࣪). These model is established directly from patient tissue, represent the tissue of origin and faithfully recapitulate patient disease in vitro and can be propagated for drug testing in a matter of weeks. PDOs bridges the gap between the lab and the clinic and effectively bring a “patient in the lab.” In this study we aimed to validate the predictive value of PDOs in the stratification of metastatic CRC (mCRC) patients for treatment with chemotherapeutic agents. PDOs from mCRC tissues were established following our optimized procedures and drug screening was performed. Clinical response was compared with PDO drug response and the best predicting drug response parameters (growth rate (GR), GRmax, GR50 and area under the curve) were identified. The patient response was evaluated by the percentage of change in size of the target lesions on response scans (% size change), best Response Evaluation Criteria in Solid Tumors (RECIST) response and progression-free survival (PFS). Importantly, we validated the predictive value of organoids towards fluorouracil (5-FU). We are validating these results in a large trial. Current efforts to further expand our PDO and drug sensitivity biobank will enable the implementation of the personalized HUB Organoid Technology to accurate and fast predict of the treatment response to improve clinical outcome of mCRC patients. Citation Format: Carla S. Verissimo, Lidwien Smabers, Emerens Wensink, Esmee Koedoot, Maarten Huismans, Celia Higuera Barón, Ricardo Korporaal, Emma Teal, Katerina-Chara Pitsa, Edwin van Oosten, Roshni Nair, Liselot Valkenburg, Geert Cirkel, Anneta Brousali, Jorieke Salij, René Overmeer, Manon Braat, Sjoerd Elias, Robert Vries, Onno Kranenburg, Miriam Koopman, Sylvia F. Boj, Jeanine Roodhart. Patient derived organoids predict clinical response: A patient in the lab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4112.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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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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