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Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Pediatric acute lymphoblastic leukemia (ALL) has cure rates exceeding 80%, yet approximately 20% of patients experience relapse, for whom treatment remains challenging. The biological and clinical heterogeneity of ALL complicates therapeutic decision-making, especially in relapse. A functional, patient-specific tool to identify effective drugs could complement current stratification approaches and potentially optimize therapy selection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We developed ELDA (\n                      <jats:italic>Ex vivo<\/jats:italic>\n                      Leukemia Drug Advisor), a novel drug screening platform based on time-lapse bright-field microscopy. Primary ALL cells were co-cultured with human bone marrow stromal cells in a three-dimensional collagen matrix, replicating a physiologically relevant microenvironment. Candidate drugs were added, and wells were imaged every 30\u00a0min for 96\u00a0h. A custom image analysis algorithm quantified viable cells by detecting subtle cell membrane movements, enabling real-time monitoring of treatment response.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and discussion<\/jats:title>\n                    <jats:p>\n                      ELDA\u2019s results demonstrated strong concordance with established cytotoxicity assays, including MTT and Calcein-AM, validating its performance\n                      <jats:italic>in vitro<\/jats:italic>\n                      . Drug profiling of 25 pediatric ALL samples against a panel of 50 clinically relevant and experimental agents revealed distinct sensitivity and resistance patterns for each patient. Notably, heterogeneity was observed even among cases sharing the same genetic alterations, underscoring the limitations of genotype-based therapeutic predictions alone. Drugs with similar mechanisms of action exhibited correlated activity profiles, confirming the biological consistency of the assay. Importantly, ELDA-predicted differences in sensitivity to dexamethasone and vincristine were validated\n                      <jats:italic>in vivo<\/jats:italic>\n                      , further supporting its translational relevance. ELDA is a standardized and validated\n                      <jats:italic>ex vivo<\/jats:italic>\n                      drug screening methodology capable of generating individualized drug response profiles for pediatric ALL. Beyond its investigational potential in precision oncology, ELDA offers a platform for preclinical evaluation of novel agents and drug combinations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1685447","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T05:22:46Z","timestamp":1773984166000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["ELDA: real-time functional drug profiling in acute lymphoblastic leukemia"],"prefix":"10.3389","volume":"16","author":[{"given":"Samara Sousa","family":"Mariano","sequence":"first","affiliation":[{"name":"Leukemia biology laboratory, Boldrini Children\u2019s Center","place":["Campinas, Brazil"]},{"name":"Graduate Program in Genetics and Molecular Biology, Institute of Biology, University of Campinas","place":["Campinas, Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leandro Henrique de Paula","family":"Assis","sequence":"additional","affiliation":[{"name":"Leukemia biology laboratory, Boldrini Children\u2019s Center","place":["Campinas, Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana Ronchi","family":"Correa","sequence":"additional","affiliation":[{"name":"Leukemia biology laboratory, Boldrini Children\u2019s Center","place":["Campinas, Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael Renatino","family":"Canevarolo","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Physiology, H. 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