{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T15:04:37Z","timestamp":1780499077538,"version":"3.54.1"},"reference-count":22,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T00:00:00Z","timestamp":1780185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Curesponse"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background\/Objectives: Providing optimized and accurate treatment to cancer patients remains a major challenge in oncology care. The emergence of precision medicine tools to match the correct therapy to the patient has significantly advanced treatment modalities in the last few years. While genomics has been shown to be critical in selecting targeted therapies for a specific somatic mutation, the overall clinical benefit of broad genomic sequencing has been found lacking. Here, we evaluate the utility of our previously clinically validated ex vivo functional assay across different treatment scenarios, demonstrating its ability to transform predicted non-responders into predicted responders, rule out ineffective treatments, provide multiple treatment options, and validate physician choices. Methods: The evaluation was performed on a post-market surveillance study analyzing 312 patients, from which 278 patients had successful test reports (an 89.1% test success rate), with clinical outcomes available from 45 of those patients. Results: We show that in the group of patients with clinical response data, the tests yield a PPV of 91.18% and NPV of 90.91% with clinical utility impacting physician decision in 51.1% of cases. Further analysis of the entire cohort showed the potential of clinical utility to reach up to 59.3% on a large group of patients. Conclusions: The accurate prediction of patient response using the test suggests the potential for the platform to improve patient treatment in clinical practice by reducing ineffective drug use and optimizing personalized patient drug regiments.<\/jats:p>","DOI":"10.3390\/jpm16060298","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:11:01Z","timestamp":1780333861000},"page":"298","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Utility of an Ex Vivo Functional Test in Personalized Cancer Treatment"],"prefix":"10.3390","volume":"16","author":[{"given":"Vered","family":"Bar","sequence":"first","affiliation":[{"name":"Curesponse, Ltd., Rehovot 7670101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adi","family":"Zundelevich","sequence":"additional","affiliation":[{"name":"Curesponse, Ltd., Rehovot 7670101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1639-4684","authenticated-orcid":false,"given":"Nancy","family":"Gavert","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 7610001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Aharon","sequence":"additional","affiliation":[{"name":"Curesponse, Ltd., Rehovot 7670101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bassima","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Curesponse, Ltd., Rehovot 7670101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kosenko","sequence":"additional","affiliation":[{"name":"Curesponse, Ltd., Rehovot 7670101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Neev","sequence":"additional","affiliation":[{"name":"Curesponse, Ltd., Rehovot 7670101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronen","family":"Viner","sequence":"additional","affiliation":[{"name":"Curesponse, Ltd., Rehovot 7670101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravid","family":"Straussman","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 7610001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raanan","family":"Berger","sequence":"additional","affiliation":[{"name":"Curesponse, Ltd., Rehovot 7670101, Israel"},{"name":"Department of Oncology, Sheba Medical Center, Ramat Gan 5265601, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth J.","family":"Salpeter","sequence":"additional","affiliation":[{"name":"Curesponse, Ltd., Rehovot 7670101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6169","DOI":"10.1038\/ncomms7169","article-title":"Predicting clinical response to anticancer drugs using an ex vivo platform that captures tumour heterogeneity","volume":"6","author":"Majumder","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/nrclinonc.2016.164","article-title":"Targeted therapies: What have we learned from SHIVA?","volume":"13","author":"Kurzrock","year":"2016","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"102029","DOI":"10.1016\/j.eclinm.2023.102029","article-title":"Usefulness and real-world outcomes of next generation sequencing testing in patients with cancer: An observational study on the impact of selection based on clinical judgement","volume":"60","author":"Colomer","year":"2023","journal-title":"eClinicalMedicine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/nrc4015","article-title":"Precision medicine for cancer with next-generation functional diagnostics","volume":"15","author":"Friedman","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"FSO190","DOI":"10.4155\/fsoa-2017-0003","article-title":"Ex Vivo tumor culture systems for functional drug testing and therapy response prediction","volume":"3","author":"Meijer","year":"2017","journal-title":"Future Sci. OA"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"van den Tempel, N., Naipal, K.A.T., Raams, A., van Gent, D.C., Franckena, M., Boormans, J.L., and Kanaar, R. (2018). Ex vivo assays to predict enhanced chemosensitization by hyperthermia in urothelial cancer of the bladder. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0209101"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5798","DOI":"10.1038\/s41598-020-62848-5","article-title":"Optimization of cell viability assays to improve replicability and reproducibility of cancer drug sensitivity screens","volume":"10","author":"Larsson","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.ccr.2005.05.024","article-title":"Therapeutic targeting of the tumor microenvironment","volume":"7","author":"Joyce","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/s43018-021-00325-2","article-title":"Ex vivo organotypic cultures for synergistic therapy prioritization identify patient-specific responses to combined MEK and Src inhibition in colorectal cancer","volume":"3","author":"Gavert","year":"2022","journal-title":"Nat. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1080\/15384047.2018.1450114","article-title":"Ev vivo organ culture as potential prioritization tool for breast cancer targeted therapy","volume":"19","author":"Grinshpun","year":"2018","journal-title":"Cancer Biol. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3296","DOI":"10.1038\/s41467-020-17090-y","article-title":"Predicting and affecting response to cancer therapy based on pathway-level biomarkers","volume":"11","author":"Gavert","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Golan, S., Bar, V., Salpeter, S.J., Neev, G., Creiderman, G., Kedar, D., Aharon, S., Turovsky, L., Zundelevich, A., and Shahar, H. (2023). A clinical evaluation of an ex vivo organ culture system to predict patient response to cancer therapy. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1221484"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41698-021-00234-8","article-title":"An analysis of research biopsy core variability from over 5000 prospectively collected core samples","volume":"5","author":"Bhamidipati","year":"2021","journal-title":"npj Precis. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2647","DOI":"10.1200\/JCO.21.00079","article-title":"Pembrolizumab Plus Ipilimumab Following Anti-PD-1\/L1 Failure in Melanoma","volume":"39","author":"Olson","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"FSO600","DOI":"10.2144\/fsoa-2020-0024","article-title":"Estimation of US patients with cancer who may respond to cytotoxic chemotherapy","volume":"6","author":"Maldonado","year":"2020","journal-title":"Future Sci. OA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1001\/jamainternmed.2019.0583","article-title":"An Overview of Cancer Drugs Approved by the US Food and Drug Administration Based on the Surrogate End Point of Response Rate","volume":"179","author":"Chen","year":"2019","journal-title":"JAMA Intern. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1158\/1535-7163.MCT-11-0233","article-title":"A pilot clinical study of treatment guided by personalized tumorgrafts in patients with advanced cancer","volume":"10","author":"Hidalgo","year":"2011","journal-title":"Mol. Cancer Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1158\/2159-8290.CD-16-1154","article-title":"Personalized In Vitro and In Vivo Cancer Models to Guide Precision Medicine","volume":"7","author":"Pauli","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1126\/science.aao2774","article-title":"Patient-derived organoids model treatment response of metastatic gastrointestinal cancers","volume":"359","author":"Vlachogiannis","year":"2018","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/S1470-2045(15)00188-6","article-title":"Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): A multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial","volume":"16","author":"Delord","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e2311181","DOI":"10.1001\/jamanetworkopen.2023.11181","article-title":"Assessment of Tumor Mutational Burden and Outcomes in Patients with Diverse Advanced Cancers Treated with Immunotherapy","volume":"6","author":"Aggarwal","year":"2023","journal-title":"JAMA Netw. Open"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e010132","DOI":"10.1136\/jitc-2024-010132","article-title":"Predictive value of ENLIGHT-DP in patients with metastatic lung adenocarcinoma treated with immune checkpoint inhibitors and platinum chemotherapy directly from histopathology slides using inferred transcriptomics","volume":"13","author":"Arnon","year":"2025","journal-title":"J. Immunother. 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