{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T01:19:57Z","timestamp":1792545597423,"version":"4.5.0"},"reference-count":90,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006742","name":"Cooperativa de Ensino Superior Polit\u00e9cnico e Universit\u00e1rio","doi-asserted-by":"publisher","award":["TARGET4OC-GI2-CESPU-2025"],"award-info":[{"award-number":["TARGET4OC-GI2-CESPU-2025"]}],"id":[{"id":"10.13039\/501100006742","id-type":"DOI","asserted-by":"publisher"}]},{"award":["TARGET4OC-GI2-CESPU-2025"],"award-info":[{"award-number":["TARGET4OC-GI2-CESPU-2025"]}],"id":[{"id":"https:\/\/ror.org\/00w7bj245","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ovarian cancer (OC) remains one of the leading causes of gynecologic cancer mortality, largely due to late diagnosis, frequent relapse, and the emergence of chemoresistance. An important but often-overlooked contributor to treatment failure is the heterogeneous penetration of anticancer drugs within tumors. Structural and biochemical barriers\u2014including abnormal vasculature, elevated interstitial pressure, dense extracellular matrix, drug efflux transporters, and malignant ascites\u2014generate steep intratumoral concentration gradients that conventional preclinical models fail to capture. As a result, systemic pharmacokinetic measurements frequently provide limited insight into tumor-level drug exposure. Patient-derived organoids (PDOs) have emerged as physiologically relevant 3D models that preserve the genetic, architectural, and functional characteristics of the original tumor. These systems enable controlled investigation of pharmacokinetic and pharmacodynamic processes, including drug penetration, metabolism, retention, and exposure\u2013response relationships. Adding cell-free malignant ascites supernatant enhances PDOs\u2019 ability to mimic the metastatic peritoneal microenvironment of OC. This review discusses recent advances in PDO technologies and examines how PDO-derived data can inform intratumoral pharmacokinetics and dosing strategies using physiologically based pharmacokinetic modeling and in vitro\u2013in vivo extrapolation. Emerging hybrid platforms, including organoid-on-chip systems, vascularized co-cultures, and multi-omics integration, are crucial to improve translational prediction and support precision oncology.<\/jats:p>","DOI":"10.3390\/ijms27083423","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T17:05:51Z","timestamp":1775840751000},"page":"3423","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Re-Thinking Pharmacokinetics in Ovarian Cancer: What Do Organoids Add?"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0931-1978","authenticated-orcid":false,"given":"Ana Emanuela Cisne de","family":"Lima","sequence":"first","affiliation":[{"name":"Applied Molecular Biosciences Unit (UCIBIO), Toxicologic Pathology Research Laboratory, University Institute of Health Sciences, Cooperative for Polytechnic and University Higher Education (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal"},{"name":"Associate Laboratory of Institute for Health and Bioeconomy (i4HB), University Institute of Health Sciences, Cooperative for Polytechnic and University Higher Education (IUCS-CESPU), CRL, 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4733-5778","authenticated-orcid":false,"given":"Mariana","family":"Nunes","sequence":"additional","affiliation":[{"name":"Applied Molecular Biosciences Unit (UCIBIO), Toxicologic Pathology Research Laboratory, University Institute of Health Sciences, Cooperative for Polytechnic and University Higher Education (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal"},{"name":"Associate Laboratory of Institute for Health and Bioeconomy (i4HB), University Institute of Health Sciences, Cooperative for Polytechnic and University Higher Education (IUCS-CESPU), CRL, 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4613-1917","authenticated-orcid":false,"given":"Cristina P. R.","family":"Xavier","sequence":"additional","affiliation":[{"name":"Applied Molecular Biosciences Unit (UCIBIO), Toxicologic Pathology Research Laboratory, University Institute of Health Sciences, Cooperative for Polytechnic and University Higher Education (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal"},{"name":"Associate Laboratory of Institute for Health and Bioeconomy (i4HB), University Institute of Health Sciences, Cooperative for Polytechnic and University Higher Education (IUCS-CESPU), CRL, 4585-116 Gandra, Portugal"},{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4091-2226","authenticated-orcid":false,"given":"Sara","family":"Ricardo","sequence":"additional","affiliation":[{"name":"Applied Molecular Biosciences Unit (UCIBIO), Toxicologic Pathology Research Laboratory, University Institute of Health Sciences, Cooperative for Polytechnic and University Higher Education (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal"},{"name":"Associate Laboratory of Institute for Health and Bioeconomy (i4HB), University Institute of Health Sciences, Cooperative for Polytechnic and University Higher Education (IUCS-CESPU), CRL, 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/s41571-024-00881-3","article-title":"Global Epidemiology of Epithelial Ovarian Cancer","volume":"21","author":"Webb","year":"2024","journal-title":"Nat. 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