{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T02:53:19Z","timestamp":1781837599177,"version":"3.54.5"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003621","name":"Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["1711170584"],"award-info":[{"award-number":["1711170584"]}],"id":[{"id":"10.13039\/501100003621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003621","name":"Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["RS-2023-00225239"],"award-info":[{"award-number":["RS-2023-00225239"]}],"id":[{"id":"10.13039\/501100003621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003621","name":"Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["RS-2024-00340403"],"award-info":[{"award-number":["RS-2024-00340403"]}],"id":[{"id":"10.13039\/501100003621","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sig Transduct Target Ther"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Effective precision oncology demands integration of pharmacokinetics\/pharmacodynamics (PK\/PD) profiling with tumor-specific genomic features. Here, we present a personalized treatment model using a patient-derived Networking Organoid Culture System (NOCS) composed of intestinal, liver, and kidney organoids differentiated from induced pluripotent stem cells (iPSCs) of an\n                    <jats:italic>NF1<\/jats:italic>\n                    -mutant breast cancer patient. This multi-organoid system enabled individualized assessment of drug absorption, distribution, metabolism, and excretion. Integrative genomic and pathway analyses uncovered therapeutic vulnerabilities, including responsiveness to a novel exon skipping therapy targeting\n                    <jats:italic>NF1<\/jats:italic>\n                    . PK\/PD-guided screening on the NOCS prioritized Paxalisib, which, when combined with the exon skipping approach, demonstrated synergistic anticancer efficacy in patient-derived tumor models. These findings establish a clinically relevant framework that integrates multi-organ PK\/PD modeling with genotype-driven therapeutic strategies, highlighting the potential of combining targeted gene correction with small-molecule therapy for personalized treatment. This platform offers broad applicability in precision oncology and drug development across diverse genetic contexts.\n                  <\/jats:p>","DOI":"10.1038\/s41392-026-02595-7","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:02:02Z","timestamp":1772668922000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Personalized pharmacokinetic\u2013pharmacodynamic guided therapy via an induced pluripotent stem cell\u2013derived multi-organoid platform in NF1-mutant breast cancer"],"prefix":"10.1038","volume":"11","author":[{"given":"Jung Hwa","family":"Lim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seon Ju","family":"Mun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Mi","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Dong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Jin","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Yoon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye Seul","family":"Son","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sugi","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae Soo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaeseo","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Jeong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8242-9390","authenticated-orcid":false,"given":"Hyun-Soo","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myung Jin","family":"Son","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7590-8812","authenticated-orcid":false,"given":"Mi-Young","family":"Son","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cho-Rok","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,5]]},"reference":[{"key":"2595_CR1","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/nrc1653","volume":"5","author":"JB Rubin","year":"2005","unstructured":"Rubin, J. B. & Gutmann, D. H. Neurofibromatosis type 1\u2014a model for nervous system tumour formation?. Nat. Rev. Cancer 5, 557\u2013564 (2005).","journal-title":"Nat. Rev. Cancer"},{"key":"2595_CR2","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/nrc3911","volume":"15","author":"N Ratner","year":"2015","unstructured":"Ratner, N. & Miller, S. J. A RASopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor. Nat. Rev. Cancer 15, 290\u2013301 (2015).","journal-title":"Nat. Rev. Cancer"},{"key":"2595_CR3","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1080\/13543784.2023.2263836","volume":"32","author":"J-S Giraud","year":"2023","unstructured":"Giraud, J.-S., Bieche, I., Pasmant, E. & Tlemsani, C. NF1 alterations in cancers: therapeutic implications in precision medicine. Expert Opin. Investig. Drugs 32, 941\u2013957 (2023).","journal-title":"Expert Opin. Investig. Drugs"},{"key":"2595_CR4","doi-asserted-by":"crossref","unstructured":"Moon, A. in Translational Research in Breast Cancer 81\u2013101 (Springer, 2021).","DOI":"10.1007\/978-981-32-9620-6_4"},{"key":"2595_CR5","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1158\/1078-0432.CCR-18-4044","volume":"26","author":"A Pearson","year":"2020","unstructured":"Pearson, A. et al. Inactivating NF1 mutations are enriched in advanced breast cancer and contribute to endocrine therapy resistance. Clin. Cancer Res. 26, 608\u2013622 (2020).","journal-title":"Clin. Cancer Res."},{"key":"2595_CR6","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1136\/jmedgenet-2018-105599","volume":"56","author":"IM Frayling","year":"2019","unstructured":"Frayling, I. M. et al. Breast cancer risk in neurofibromatosis type 1 is a function of the type of NF1 gene mutation: a new genotype-phenotype correlation. J. Med. Genet. 56, 209\u2013219 (2019).","journal-title":"J. Med. Genet."},{"key":"2595_CR7","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1007\/s11912-024-01527-4","volume":"26","author":"B Na","year":"2024","unstructured":"Na, B., Shah, S. R. & Vasudevan, H. N. Past, present, and future therapeutic strategies for NF-1-Associated tumors. Curr. Oncol. Rep. 26, 706\u2013713 (2024).","journal-title":"Curr. Oncol. Rep."},{"key":"2595_CR8","doi-asserted-by":"publisher","first-page":"115365","DOI":"10.1016\/j.celrep.2025.115365","volume":"44","author":"D Berry","year":"2025","unstructured":"Berry, D. et al. The NF1 tumor suppressor regulates PD-L1 and immune evasion in melanoma. Cell Rep. 44, 115365 (2025).","journal-title":"Cell Rep."},{"key":"2595_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2024.101876","volume":"80","author":"RRJ House","year":"2024","unstructured":"House, R. R. J. et al. NF1 deficiency drives metabolic reprogramming in ER+ breast cancer. Mol. Metab. 80, 101876 (2024).","journal-title":"Mol. Metab."},{"key":"2595_CR10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2407745121","volume":"122","author":"SF Sait","year":"2025","unstructured":"Sait, S. F. et al. Hydroxychloroquine prevents resistance and potentiates the antitumor effect of SHP2 inhibition in NF1-associated malignant peripheral nerve sheath tumors. Proc. Natl. Acad. Sci. 122, e2407745121 (2025).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"2595_CR11","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1261\/rna.653607","volume":"13","author":"A Aartsma-Rus","year":"2007","unstructured":"Aartsma-Rus, A. & Van Ommen, G.-J. B. Antisense-mediated exon skipping: a versatile tool with therapeutic and research applications. RNA 13, 1609\u20131624 (2007).","journal-title":"RNA"},{"key":"2595_CR12","doi-asserted-by":"publisher","first-page":"14862","DOI":"10.3390\/ijms241914862","volume":"24","author":"C Pacelli","year":"2023","unstructured":"Pacelli, C., Rossi, A., Milella, M., Colombo, T. & Le Pera, L. RNA-Based Strategies for Cancer Therapy: In Silico Design and Evaluation of ASOs for Targeted Exon Skipping. Int. J. Mol. Sci. 24, 14862 (2023).","journal-title":"Int. J. Mol. Sci."},{"key":"2595_CR13","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.coph.2021.05.008","volume":"59","author":"A Jbara","year":"2021","unstructured":"Jbara, A., Siegfried, Z. & Karni, R. Splice-switching as cancer therapy. Curr. Opin. Pharmacol. 59, 140\u2013148 (2021).","journal-title":"Curr. Opin. Pharmacol."},{"key":"2595_CR14","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1158\/2159-8290.CD-19-1436","volume":"10","author":"Y Zhou","year":"2020","unstructured":"Zhou, Y. et al. Posttranslational regulation of the exon skipping machinery controls aberrant splicing in leukemia. Cancer Discov. 10, 1388\u20131409 (2020).","journal-title":"Cancer Discov."},{"key":"2595_CR15","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.stem.2020.02.011","volume":"26","author":"A Sharma","year":"2020","unstructured":"Sharma, A., Sances, S., Workman, M. J. & Svendsen, C. N. Multi-lineage human iPSC-derived platforms for disease modeling and drug discovery. Cell Stem Cell 26, 309\u2013329 (2020).","journal-title":"Cell Stem Cell"},{"key":"2595_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13619-020-00059-z","volume":"9","author":"Y Li","year":"2020","unstructured":"Li, Y., Tang, P., Cai, S., Peng, J. & Hua, G. Organoid based personalized medicine: from bench to bedside. Cell Regen. 9, 1\u201333 (2020).","journal-title":"Cell Regen."},{"key":"2595_CR17","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.cotox.2021.08.006","volume":"28","author":"D van Berlo","year":"2021","unstructured":"van Berlo, D. et al. Stem cells, organoids, and organ-on-a-chip models for personalized in vitro drug testing. Curr. Opin. Toxicol. 28, 7\u201314 (2021).","journal-title":"Curr. Opin. Toxicol."},{"key":"2595_CR18","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1038\/s41580-020-0259-3","volume":"21","author":"J Kim","year":"2020","unstructured":"Kim, J., Koo, B.-K. & Knoblich, J. A. Human organoids: model systems for human biology and medicine. Nat. Rev. Mol. Cell Biol. 21, 571\u2013584 (2020).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2595_CR19","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1111\/cts.13132","volume":"15","author":"KP Van Ness","year":"2022","unstructured":"Van Ness, K. P., Cesar, F., Yeung, C. K., Himmelfarb, J. & Kelly, E. J. Microphysiological systems in absorption, distribution, metabolism, and elimination sciences. Clin. Transl. Sci. 15, 9\u201342 (2022).","journal-title":"Clin. Transl. Sci."},{"key":"2595_CR20","doi-asserted-by":"publisher","first-page":"045029","DOI":"10.1088\/1758-5090\/abb652","volume":"12","author":"KH Noh","year":"2020","unstructured":"Noh, K. H. et al. A new experimental model to study human drug responses. Biofabrication 12, 045029 (2020).","journal-title":"Biofabrication"},{"key":"2595_CR21","doi-asserted-by":"publisher","first-page":"210333","DOI":"10.1098\/rsob.210333","volume":"12","author":"T Shroff","year":"2022","unstructured":"Shroff, T. et al. Studying metabolism with multi-organ chips: new tools for disease modelling, pharmacokinetics and pharmacodynamics. Open Biology 12, 210333 (2022).","journal-title":"Open Biology"},{"key":"2595_CR22","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1557\/mrc.2018.148","volume":"8","author":"V Palaninathan","year":"2018","unstructured":"Palaninathan, V. et al. Multi-organ on a chip for personalized precision medicine. MRS Commun. 8, 652\u2013667 (2018).","journal-title":"MRS Commun."},{"key":"2595_CR23","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1038\/s41576-022-00466-9","volume":"23","author":"DE Ingber","year":"2022","unstructured":"Ingber, D. E. Human organs-on-chips for disease modelling, drug development and personalized medicine. Nat. Rev. Genet. 23, 467\u2013491 (2022).","journal-title":"Nat. Rev. Genet."},{"key":"2595_CR24","doi-asserted-by":"publisher","first-page":"4280","DOI":"10.3390\/ijms23084280","volume":"23","author":"R Rodrigues","year":"2022","unstructured":"Rodrigues, R., Duarte, D. & Vale, N. Drug repurposing in cancer therapy: influence of patient\u2019s genetic background in breast cancer treatment. Int. J. Mol. Sci. 23, 4280 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"2595_CR25","doi-asserted-by":"publisher","first-page":"100100","DOI":"10.1016\/j.xhgg.2022.100100","volume":"3","author":"C Auwerx","year":"2022","unstructured":"Auwerx, C., Sadler, M. C., Reymond, A. & Kutalik, Z. From pharmacogenetics to pharmaco-omics: Milestones and future directions. Hum. Genet. Genom. Adv. 3, 100100 (2022).","journal-title":"Hum. Genet. Genom. Adv."},{"key":"2595_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12885-021-07782-z","volume":"21","author":"J Fraisse","year":"2021","unstructured":"Fraisse, J., Dinart, D., Tosi, D., Bellera, C. & Mollevi, C. Optimal biological dose: a systematic review in cancer phase I clinical trials. BMC Cancer 21, 1\u201310 (2021).","journal-title":"BMC Cancer"},{"key":"2595_CR27","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abh1586","volume":"7","author":"O Kwon","year":"2021","unstructured":"Kwon, O. et al. The development of a functional human small intestinal epithelium model for drug absorption. Sci. Adv. 7, eabh1586 (2021).","journal-title":"Sci. Adv."},{"key":"2595_CR28","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1016\/j.jhep.2019.06.030","volume":"71","author":"SJ Mun","year":"2019","unstructured":"Mun, S. J. et al. Generation of expandable human pluripotent stem cell-derived hepatocyte-like liver organoids. J. Hepatol. 71, 970\u2013985 (2019).","journal-title":"J. Hepatol."},{"key":"2595_CR29","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1016\/j.tibtech.2020.11.014","volume":"39","author":"N Picollet-D\u2019hahan","year":"2021","unstructured":"Picollet-D\u2019hahan, N., Zuchowska, A., Lemeunier, I. & Le Gac, S. Multiorgan-on-a-chip: a systemic approach to model and decipher inter-organ communication. Trends Biotechnol. 39, 788\u2013810 (2021).","journal-title":"Trends Biotechnol."},{"key":"2595_CR30","doi-asserted-by":"publisher","first-page":"111868","DOI":"10.1016\/j.biopha.2021.111868","volume":"141","author":"H-F Zhang","year":"2021","unstructured":"Zhang, H.-F. et al. The mechanisms of renin\u2013angiotensin system in hepatocellular carcinoma: From the perspective of liver fibrosis, HCC cell proliferation, metastasis and angiogenesis, and corresponding protection measures. Biomed. Pharmacother. 141, 111868 (2021).","journal-title":"Biomed. Pharmacother."},{"key":"2595_CR31","doi-asserted-by":"publisher","first-page":"e200","DOI":"10.1016\/j.clbc.2023.02.005","volume":"23","author":"K Yan","year":"2023","unstructured":"Yan, K., Gao, Y. & Heller, S. L. Breast cancer screening utilization and outcomes in women with neurofibromatosis Type 1. Clin. Breast Cancer 23, e200\u2013e205 (2023).","journal-title":"Clin. Breast Cancer"},{"key":"2595_CR32","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1038\/s41436-019-0651-6","volume":"22","author":"DGR Evans","year":"2020","unstructured":"Evans, D. G. R. et al. Breast cancer in neurofibromatosis 1: survival and risk of contralateral breast cancer in a five country cohort study. Genet. Med. 22, 398\u2013406 (2020).","journal-title":"Genet. Med."},{"key":"2595_CR33","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1158\/1541-7786.MCR-13-0212","volume":"11","author":"X Chen","year":"2013","unstructured":"Chen, X. et al. Dual inhibition of PI3K and mTOR mitigates compensatory AKT activation and improves tamoxifen response in breast cancer. Mol. Cancer Res. 11, 1269\u20131278 (2013).","journal-title":"Mol. Cancer Res."},{"key":"2595_CR34","doi-asserted-by":"publisher","first-page":"531","DOI":"10.4143\/crt.2022.221","volume":"55","author":"JW Kim","year":"2023","unstructured":"Kim, J. W. et al. PIK3CA mutation is associated with poor response to HER2-targeted therapy in breast cancer patients. Cancer Res. Treat. J. Korean Cancer Assoc. 55, 531\u2013541 (2023).","journal-title":"Cancer Res. Treat. J. Korean Cancer Assoc."},{"key":"2595_CR35","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1007\/s12609-015-0197-9","volume":"7","author":"IA Mayer","year":"2015","unstructured":"Mayer, I. A. Clinical implications of mutations in the PI3K pathway in HER2+ breast cancer: prognostic or predictive?. Curr. Breast Cancer Rep. 7, 210\u2013214 (2015).","journal-title":"Curr. Breast Cancer Rep."},{"key":"2595_CR36","first-page":"1317","volume":"32","author":"D Lesman","year":"2021","unstructured":"Lesman, D., Rodriguez, Y., Rajakumar, D. & Wein, N. U7 snRNA, a small RNA with a big impact in gene therapy. Hum. Gene Ther. 32, 1317\u20131329 (2021).","journal-title":"Hum. Gene Ther."},{"key":"2595_CR37","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1038\/mt.2009.113","volume":"17","author":"A Goyenvalle","year":"2009","unstructured":"Goyenvalle, A., Babbs, A., van Ommen, G.-J. B., Garcia, L. & Davies, K. E. Enhanced exon-skipping induced by U7 snRNA carrying a splicing silencer sequence: Promising tool for DMD therapy. Mol. Ther. 17, 1234\u20131240 (2009).","journal-title":"Mol. Ther."},{"key":"2595_CR38","doi-asserted-by":"publisher","first-page":"e3321","DOI":"10.1002\/jgm.3321","volume":"23","author":"A Gadgil","year":"2021","unstructured":"Gadgil, A. & Raczy\u0144ska, K. D. U7 snRNA: A tool for gene therapy. J. Gene Med. 23, e3321 (2021).","journal-title":"J. Gene Med."},{"key":"2595_CR39","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1016\/j.celrep.2013.11.012","volume":"5","author":"S Tisdale","year":"2013","unstructured":"Tisdale, S. et al. SMN is essential for the biogenesis of U7 small nuclear ribonucleoprotein and 3\u2032-end formation of histone mRNAs. Cell Rep. 5, 1187\u20131195 (2013).","journal-title":"Cell Rep."},{"key":"2595_CR40","doi-asserted-by":"publisher","unstructured":"Wallis, D. et al. Exon skipping as a therapeutic for neurofibromatosis Type I. Research Square Preprint  https:\/\/doi.org\/10.21203\/rs.3.rs-751331\/v1 (2021).","DOI":"10.21203\/rs.3.rs-751331\/v1"},{"key":"2595_CR41","doi-asserted-by":"publisher","first-page":"533","DOI":"10.2147\/DDDT.S97635","volume":"11","author":"KRQ Lim","year":"2017","unstructured":"Lim, K. R. Q., Maruyama, R. & Yokota, T. Eteplirsen in the treatment of Duchenne muscular dystrophy. Drug Design Dev. Ther. 11, 533\u2013545 (2017).","journal-title":"Drug Design Dev. Ther."},{"key":"2595_CR42","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1038\/nrc.2016.51","volume":"16","author":"H Dvinge","year":"2016","unstructured":"Dvinge, H., Kim, E., Abdel-Wahab, O. & Bradley, R. K. RNA splicing factors as oncoproteins and tumour suppressors. Nat. Rev. Cancer 16, 413\u2013430 (2016).","journal-title":"Nat. Rev. Cancer"},{"key":"2595_CR43","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.875372","volume":"13","author":"X Wu","year":"2022","unstructured":"Wu, X. et al. Recent advances in dual PI3K\/mTOR inhibitors for tumour treatment. Front. Pharmacol. 13, 875372 (2022).","journal-title":"Front. Pharmacol."},{"key":"2595_CR44","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1080\/00498254.2024.2415103","volume":"54","author":"L Salphati","year":"2024","unstructured":"Salphati, L. et al. Preclinical assessment of the PI3K\u03b1 selective inhibitor inavolisib and prediction of its pharmacokinetics and efficacious dose in human. Xenobiotica 54, 808\u2013820 (2024).","journal-title":"Xenobiotica"},{"key":"2595_CR45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1358\/dof.2022.47.1.3349022","volume":"47","author":"Q Chen","year":"2022","unstructured":"Chen, Q. et al. Paxalisib. PI3K\/mTOR inhibitor, Treatment of gliomas. Drugs of the Future 47, 1\u20139 (2022).","journal-title":"Drugs of the Future"},{"key":"2595_CR46","doi-asserted-by":"publisher","first-page":"S193","DOI":"10.1016\/j.ijrobp.2024.07.2248","volume":"120","author":"B Imber","year":"2024","unstructured":"Imber, B. et al. Multi-Center Phase I Study of Concurrent Paxalisib and Radiation Therapy in Patients with Solid Tumor Brain Metastases (BM) or Leptomeningeal Metastases (LM) Harboring PI3K Pathway Mutations. Int. J. Radiat. Oncol., Biol., Phys. 120, S193 (2024).","journal-title":"Int. J. Radiat. Oncol., Biol., Phys."},{"key":"2595_CR47","doi-asserted-by":"publisher","first-page":"e02044","DOI":"10.1002\/adhm.202502044","volume":"14","author":"JH Lim","year":"2025","unstructured":"Lim, J. H. et al. Induction of nephron-ductal dual lineages via early retinoic acid signaling establishes a platform for fully patterned kidney organoids. Adv. Healthcare Mater. 14, e02044 (2025).","journal-title":"Adv. Healthcare Mater."}],"container-title":["Signal Transduction and Targeted Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02595-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02595-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02595-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:02:11Z","timestamp":1772668931000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02595-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,5]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2595"],"URL":"https:\/\/doi.org\/10.1038\/s41392-026-02595-7","relation":{},"ISSN":["2059-3635"],"issn-type":[{"value":"2059-3635","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,5]]},"assertion":[{"value":"22 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 January 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 March 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that Cho-Rok Jung is a co-inventor on Patent (US11,732,232 B2), which is related to the cell culture system used in this study. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"79"}}