{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T05:52:00Z","timestamp":1791525120949,"version":"4.3.4"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>This study explored pharmacokinetic and pharmacodynamic factors associated with circulating vascular endothelial growth factor (VEGF) dynamics during bevacizumab treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A secondary analysis was conducted using data from 74 patients with breast, ovarian, cervical, non-small cell lung, or colorectal cancer. Paired pre- and post-infusion serum concentrations of bevacizumab and VEGF were measured by ELISA. Exploratory dimensionality-reduction methods and supervised tree-based models were applied. Artificial neural networks were used only as a complementary exploratory analysis on the same dataset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The main outcome of the analysis was VEGF_D, the absolute difference between the paired VEGF concentrations. The supervised models did not perform above the naive three-class benchmark; therefore, their variable-importance outputs were treated as secondary, model-specific, and hypothesis-generating observations. The results show exploratory model patterns of bevacizumab exposure and circulating VEGF dynamics. We did not assess clinical efficacy, safety results, and other dosing strategies in this study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The results do not support clinical implementation, personalized dosing, or treatment optimization and need to be confirmed in large independent cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1899527","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T05:33:31Z","timestamp":1791524011000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploratory machine-learning analysis of bevacizumab exposure and circulating VEGF dynamics in patients with cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Ileana","family":"Theofili","sequence":"first","affiliation":[{"name":"Department of Pharmacy, National and Kapodistrian University of Athens","place":["Athens, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Liolis","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Patras","place":["Patras, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelos","family":"Koutras","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Patras","place":["Patras, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vangelis D.","family":"Karalis","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, National and Kapodistrian University of Athens","place":["Athens, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Sivolapenko","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Patras","place":["Patras, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1938","DOI":"10.1002\/jcb.30344","article-title":"Molecular mechanism of VEGF and its role in pathological angiogenesis","volume":"123","author":"Ahmad","year":"2022","journal-title":"J. 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