{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T20:48:08Z","timestamp":1794084488301,"version":"4.8.0"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T00:00:00Z","timestamp":1708992000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T00:00:00Z","timestamp":1708992000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"HUB Organoids B.V."},{"DOI":"10.13039\/100008470","name":"Cancer Genomics Center","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008470","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Exp Clin Cancer Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The inability to predict treatment response of colorectal cancer patients results in unnecessary toxicity, decreased efficacy and survival. Response testing on patient-derived organoids (PDOs) is a promising biomarker for treatment efficacy. The aim of this study is to optimize PDO drug screening methods for correlation with patient response and explore the potential to predict responses to standard chemotherapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We optimized drug screen methods on 5\u201311 PDOs per condition of the complete set of 23 PDOs from patients treated for metastatic colorectal cancer (mCRC). PDOs were exposed to 5-fluorouracil (5-FU), irinotecan- and oxaliplatin-based chemotherapy. We compared medium with and without N-acetylcysteine (NAC), different readouts and different combination treatment set-ups to capture the strongest association with patient response. We expanded the screens using the optimized methods for all PDOs. Organoid sensitivity was correlated to the patient\u2019s response, determined by % change in the size of target lesions. We assessed organoid sensitivity in relation to prior exposure to chemotherapy, mutational status and sidedness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Drug screen optimization involved excluding N-acetylcysteine from the medium and biphasic curve fitting for 5-FU &amp; oxaliplatin combination screens. CellTiter-Glo measurements were comparable with CyQUANT and did not affect the correlation with patient response. Furthermore, the correlation improved with application of growth rate metrics, when 5-FU &amp; oxaliplatin was screened in a ratio, and 5-FU &amp; SN-38 using a fixed dose of SN-38. Area under the curve was the most robust drug response curve metric. After optimization, organoid and patient response showed a correlation coefficient of 0.58 for 5-FU (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096, 95% CI -0.44,0.95), 0.61 for irinotecan- (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910, 95% CI -0.03,0.90) and 0.60 for oxaliplatin-based chemotherapy (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200911, 95% CI -0.01,0.88). Median progression-free survival of patients with resistant PDOs to oxaliplatin-based chemotherapy was significantly shorter than sensitive PDOs (3.3 vs 10.9\u2009months,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.007). Increased resistance to 5-FU in patients with prior exposure to 5-FU\/capecitabine was adequately reflected in PDOs (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study emphasizes the critical impact of the screening methods for determining correlation between PDO drug screens and mCRC patient outcomes. Our 5-step optimization strategy provides a basis for future research on the clinical utility of PDO screens.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13046-024-02980-6","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T04:04:08Z","timestamp":1709006648000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Organoids as a biomarker for personalized treatment in metastatic colorectal cancer: drug screen optimization and correlation with patient response"],"prefix":"10.1186","volume":"43","author":[{"given":"Lidwien P.","family":"Smabers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emerens","family":"Wensink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla S.","family":"Verissimo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esmee","family":"Koedoot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina-Chara","family":"Pitsa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten A.","family":"Huismans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Higuera Bar\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayke","family":"Doorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liselot B.","family":"Valkenburg-van Iersel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert A.","family":"Cirkel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneta","family":"Brousali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Overmeer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Koopman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon N.","family":"Braat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bas","family":"Penning de Vries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sjoerd G.","family":"Elias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert G.","family":"Vries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onno","family":"Kranenburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia F.","family":"Boj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanine M.","family":"Roodhart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,27]]},"reference":[{"issue":"8","key":"2980_CR1","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1093\/annonc\/mdw206","volume":"27","author":"K Yamazaki","year":"2016","unstructured":"Yamazaki K, Nagase M, Tamagawa H, Ueda S, Tamura T, Murata K, et al. 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This research was performed under the HUB-Cancer biobanking protocol and OPTIC protocol. The Biobank Research Ethics Committee of the UMC Utrecht (TCBio) approved the biobanking protocol: 12\u2013093 HUB-Cancer. The medical ethical committee of the University Medical Center Utrecht (UMCU) approved the prospective clinical trial Organoids to Predict Therapy Response In Colorectal Cancer (OPTIC #17\u2013356 [\n                      \n                      ]). All donors participating in this study signed informed consent. The study was performed in accordance with the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Miriam Koopman reports institutional financial interests with Amgen, Bayer, Bristol-Myers Squibb, Merck-Serono, Nordic Pharma, Pierre Fabre, Servier, Sirtex, Roche, Sanofi, and Personal Genome Diagnostics. Miriam Koopman reports the following non-financial interests: an advisory role for ZON-MW, membership of the scientific board of the Dutch Cancer Society (KWF), chairmanship of the Dutch Colorectal Cancer Group (DCCG), and principal investigator (PI) of the Prospective Dutch Colorectal Cancer (PLCRC) cohort. Jeanine Roodhart reports institutional financial interests with BMS, Pierre Fabre, Servier, Cleara, Xilis, DoMore diagnostics and HUB organoids B.V. Jeanine Roodhart reports an advisory role for Bayer, BMS, Merck-Serono, Pierre Fabre, Servier, AMGEN and board member of Foundation Hubrecht Organoid Biobank. Liselot Valkenburg-van Iersel reports financial interests with and an advisory role for Servier and Pierre Fabre. All other authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"61"}}