{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T18:06:52Z","timestamp":1789582012843,"version":"build-2803163510"},"reference-count":169,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AA026068"],"award-info":[{"award-number":["R01AA026068"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54AA030451"],"award-info":[{"award-number":["U54AA030451"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54MD012392"],"award-info":[{"award-number":["U54MD012392"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01MD017405"],"award-info":[{"award-number":["R01MD017405"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Drug repurposing can accelerate the identification of novel therapeutic candidates for rare cancers such as inflammatory breast cancer (IBC), an aggressive type with limited therapeutic options. Here, we report an experimental validation study of compounds previously identified through two computational approaches: Literature Wide Association Studies (LWAS) and Gene Reversal Rate (GRR). Candidate compounds were tested using orthogonal cell viability assays in 2D models across IBC and non-IBC cell lines. In the SUM149 IBC cell line, repurposed compounds predicted from LWAS achieved a 70% success rate, with several showing nanomolar potency, while those predicted from GRR showed a 38% success rate. Through systematic combination screening in both 2D and 3D-spheroid SUM149 models, we identified novel synergistic compound pairs targeting crosstalk between IGF-1R, EGFR and PI3K\/Akt\/mTOR pathways, with high synergy scores across multiple reference models. Using these combinations, western blott analysis revealed significant suppression in the phosphorylation of key signaling proteins and downstream effectors, while wound healing assays showed reduced cell migration with some combination treatments, suggesting effective pathway inhibition. To further validate these findings at the transcriptional level, RNA-Seq analysis in SUM149 cells confirmed that the GRR drug combinations significantly reversed the IBC gene expression signature (IBC-GES) and identified several clinically relevant genes whose expression was significantly altered. Together, these findings validate our computational predictions and identify candidate combination strategies that may help address therapeutic resistance in IBC. This integrated computational-experimental approach establishes a pipeline for systematic drug repurposing and highlights novel therapeutic combinations for further investigation.<\/jats:p>","DOI":"10.1371\/journal.pone.0339543","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:35:54Z","timestamp":1789580154000},"page":"e0339543","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["From in silico prediction to experimental validation: Identification of drugs and novel synergistic combinations that inhibit growth of inflammatory breast cancer cells"],"prefix":"10.1371","volume":"21","author":[{"given":"Esraa A.","family":"Salim","sequence":"first","affiliation":[{"name":"Biomanufacturing Research Institute and Technology Enterprise, North Carolina Central University","place":["Durham, North Carolina, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojia","family":"Ji","sequence":"additional","affiliation":[{"name":"Biomanufacturing Research Institute and Technology Enterprise, North Carolina Central University","place":["Durham, North Carolina, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Tarpley","sequence":"additional","affiliation":[{"name":"Biomanufacturing Research Institute and Technology Enterprise, North Carolina Central University","place":["Durham, North Carolina, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria S.","family":"Dixon","sequence":"additional","affiliation":[{"name":"Biomanufacturing Research Institute and Technology Enterprise, North Carolina Central University","place":["Durham, North Carolina, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weifan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Biomanufacturing Research Institute and Technology Enterprise, North Carolina Central University","place":["Durham, North Carolina, United States of America"]},{"name":"North Carolina Central University","place":["Durham, North Carolina, United States of America"],"department":["Department of Pharmaceutical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Scott","sequence":"additional","affiliation":[{"name":"Biomanufacturing Research Institute and Technology Enterprise, North Carolina Central University","place":["Durham, North Carolina, United States of America"]},{"name":"North Carolina Central University","place":["Durham, North Carolina, United States of America"],"department":["Department of Pharmaceutical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6930-4630","authenticated-orcid":true,"given":"Kevin P.","family":"Williams","sequence":"additional","affiliation":[{"name":"Biomanufacturing Research Institute and Technology Enterprise, North Carolina Central University","place":["Durham, North Carolina, United States of America"]},{"name":"North Carolina Central University","place":["Durham, North Carolina, United States of America"],"department":["Department of Pharmaceutical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"issue":"2","key":"pone.0339543.ref001","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s10549-015-3436-x","article-title":"Overall survival differences between patients with inflammatory and noninflammatory breast cancer presenting with distant metastasis at diagnosis","volume":"152","author":"TM Fouad","year":"2015","journal-title":"Breast Cancer Res Treat"},{"issue":"8","key":"pone.0339543.ref002","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/s41568-018-0010-y","article-title":"Inflammatory breast cancer biology: the tumour microenvironment is key","volume":"18","author":"B Lim","year":"2018","journal-title":"Nat Rev Cancer"},{"issue":"6","key":"pone.0339543.ref003","first-page":"351","article-title":"Inflammatory breast cancer: the disease, the biology, the treatment","volume":"60","author":"FM Robertson","year":"2010","journal-title":"CA Cancer J Clin"},{"issue":"1","key":"pone.0339543.ref004","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s10549-020-05938-2","article-title":"Incidence and survival of inflammatory breast cancer between 1973 and 2015 in the SEER database","volume":"185","author":"HG Abraham","year":"2021","journal-title":"Breast Cancer Res Treat"},{"issue":"4","key":"pone.0339543.ref005","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.ajog.2021.04.217","article-title":"Inflammatory breast cancer: early recognition and diagnosis is critical","volume":"225","author":"RH Hester","year":"2021","journal-title":"Am J Obstet Gynecol"},{"issue":"13","key":"pone.0339543.ref006","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1093\/jnci\/dji172","article-title":"Trends in inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program at the National Cancer Institute","volume":"97","author":"KW Hance","year":"2005","journal-title":"J Natl Cancer Inst"},{"key":"pone.0339543.ref007","doi-asserted-by":"crossref","DOI":"10.1053\/j.seminoncol.2007.11.017","article-title":"Inflammatory breast cancer in Tunisia: reassessment of incidence and clinicopathological features","volume-title":"Seminars in oncology","author":"H Boussen","year":"2008"},{"issue":"9","key":"pone.0339543.ref008","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1002\/cncr.25682","article-title":"Differences in survival among women with stage III inflammatory and noninflammatory locally advanced breast cancer appear early: a large population-based study","volume":"117","author":"S Dawood","year":"2011","journal-title":"Cancer"},{"issue":"1","key":"pone.0339543.ref009","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/s41598-023-50755-4","article-title":"ER+\/PR- phenotype exhibits more aggressive biological features and worse outcome compared with ER+\/PR+ phenotype in HER2-negative inflammatory breast cancer","volume":"14","author":"Y Luo","year":"2024","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0339543.ref010","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.clbc.2014.05.005","article-title":"Inflammatory breast cancer management in the national comprehensive cancer network: the disease, recurrence pattern, and outcome","volume":"15","author":"JM Matro","year":"2015","journal-title":"Clin Breast Cancer"},{"issue":"2","key":"pone.0339543.ref011","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s10549-021-06434-x","article-title":"Inflammatory breast cancer defined: proposed common diagnostic criteria to guide treatment and research","volume":"192","author":"R Jagsi","year":"2022","journal-title":"Breast Cancer Res Treat"},{"issue":"7","key":"pone.0339543.ref012","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1634\/theoncologist.2012-0039","article-title":"Inflammatory breast cancer: what we know and what we need to learn","volume":"17","author":"H Yamauchi","year":"2012","journal-title":"Oncologist"},{"issue":"3","key":"pone.0339543.ref013","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1093\/annonc\/mdq345","article-title":"International expert panel on inflammatory breast cancer: consensus statement for standardized diagnosis and treatment","volume":"22","author":"S Dawood","year":"2011","journal-title":"Ann Oncol"},{"issue":"4","key":"pone.0339543.ref014","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2026.5023","article-title":"Inflammatory Breast Cancer and Trimodality Therapy","volume":"9","author":"AB Tadros","year":"2026","journal-title":"JAMA Netw Open"},{"issue":"6","key":"pone.0339543.ref015","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1007\/s11864-023-01077-0","article-title":"Tailoring Treatment for Patients with Inflammatory Breast Cancer","volume":"24","author":"AB Newman","year":"2023","journal-title":"Curr Treat Options Oncol"},{"issue":"19","key":"pone.0339543.ref016","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1200\/JCO.2014.55.1978","article-title":"Underuse of trimodality treatment affects survival for patients with inflammatory breast cancer: an analysis of treatment and survival trends from the National Cancer Database","volume":"32","author":"NM Rueth","year":"2014","journal-title":"J Clin Oncol"},{"issue":"9","key":"pone.0339543.ref017","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.3390\/cancers12092479","article-title":"Targeting Signaling Pathways in Inflammatory Breast Cancer","volume":"12","author":"X Wang","year":"2020","journal-title":"Cancers (Basel)"},{"key":"pone.0339543.ref018","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jare.2020.08.014","article-title":"Update on systemic treatment for newly diagnosed inflammatory breast cancer","volume":"29","author":"S Chainitikun","year":"2020","journal-title":"J Adv Res"},{"issue":"2","key":"pone.0339543.ref019","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1177\/1087057114563024","article-title":"In vitro screening for drug repositioning","volume":"20","author":"GF Wilkinson","year":"2015","journal-title":"J Biomol Screen"},{"issue":"1","key":"pone.0339543.ref020","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.drudis.2021.08.002","article-title":"Evaluating the performance of drug-repurposing technologies","volume":"27","author":"J Schuler","year":"2022","journal-title":"Drug Discov Today"},{"issue":"1","key":"pone.0339543.ref021","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/s41746-022-00617-6","article-title":"Computational drug repurposing based on electronic health records: a scoping review","volume":"5","author":"N Zong","year":"2022","journal-title":"NPJ Digit Med"},{"key":"pone.0339543.ref022","first-page":"559","article-title":"Validation approaches for computational drug repurposing: a review","volume":"2023","author":"M Pillai","year":"2024","journal-title":"AMIA Annu Symp Proc"},{"issue":"1","key":"pone.0339543.ref023","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/s41392-020-00213-8","article-title":"Overcoming cancer therapeutic bottleneck by drug repurposing","volume":"5","author":"Z Zhang","year":"2020","journal-title":"Signal Transduct Target Ther"},{"issue":"1","key":"pone.0339543.ref024","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s00280-025-04822-4","article-title":"Non-oncologic to oncologic drug: A systematic review of drug repurposing in cancer","volume":"95","author":"Y Dhanush","year":"2025","journal-title":"Cancer Chemother Pharmacol"},{"issue":"15","key":"pone.0339543.ref025","doi-asserted-by":"crossref","first-page":"5076","DOI":"10.3390\/app10155076","article-title":"Computational Drug Repositioning: Current Progress and Challenges","volume":"10","author":"Y Ko","year":"2020","journal-title":"Applied Sciences"},{"issue":"3","key":"pone.0339543.ref026","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1002\/cpt.318","article-title":"Leveraging big data to transform target selection and drug discovery","volume":"99","author":"B Chen","year":"2016","journal-title":"Clin Pharmacol Ther"},{"key":"pone.0339543.ref027","doi-asserted-by":"crossref","first-page":"109043","DOI":"10.1016\/j.abb.2021.109043","article-title":"Drug repositioning based on gene expression data for human HER2-positive breast cancer","volume":"712","author":"F Khanjani","year":"2021","journal-title":"Arch Biochem Biophys"},{"issue":"17","key":"pone.0339543.ref028","doi-asserted-by":"crossref","first-page":"3933","DOI":"10.3390\/molecules25173933","article-title":"Literature-Wide Association Studies (LWAS) for a Rare Disease: Drug Repurposing for Inflammatory Breast Cancer","volume":"25","author":"X Ji","year":"2020","journal-title":"Molecules"},{"key":"pone.0339543.ref029","article-title":"Applying a Gene Reversal Rate Computational Methodology to Identify Drugs for a Rare Cancer: Inflammatory Breast Cancer","volume":"22","author":"X Ji","year":"2023","journal-title":"Cancer Inform"},{"key":"pone.0339543.ref030","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/978-1-4939-9089-4_13","article-title":"Text Mining for Drug Discovery","volume":"1939","author":"S Zheng","year":"2019","journal-title":"Methods Mol Biol"},{"key":"pone.0339543.ref031","volume-title":"Drug repurposing-molecular aspects| therapeutic applications","author":"Z Jia","year":"2021"},{"key":"pone.0339543.ref032","doi-asserted-by":"crossref","first-page":"16022","DOI":"10.1038\/ncomms16022","article-title":"Reversal of cancer gene expression correlates with drug efficacy and reveals therapeutic targets","volume":"8","author":"B Chen","year":"2017","journal-title":"Nat Commun"},{"key":"pone.0339543.ref033","article-title":"Efficient estimation of word representations in vector space.","author":"T Mikolov","year":"2013"},{"key":"pone.0339543.ref034","first-page":"2579","article-title":"Visualizing data using t-SNE","volume":"9","author":"L van der Maaten","year":"2008","journal-title":"J Mach Learn Res"},{"issue":"1","key":"pone.0339543.ref035","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/s41523-022-00431-z","article-title":"Adaptive stress response genes associated with breast cancer subtypes and survival outcomes reveal race-related differences","volume":"8","author":"M Al Abo","year":"2022","journal-title":"NPJ Breast Cancer"},{"key":"pone.0339543.ref036","doi-asserted-by":"crossref","unstructured":"Bambhroliya A, Wyhe R, Swaminathan SK, Debeb B, Reddy J, Laere S v. Gene set analysis of post-lactational mammary gland involution gene signatures in inflammatory and triple-negative breast cancer. 2018.","DOI":"10.1371\/journal.pone.0192689"},{"issue":"5","key":"pone.0339543.ref037","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.breast.2014.06.008","article-title":"Genomic profiling of inflammatory breast cancer: a review","volume":"23","author":"F Bertucci","year":"2014","journal-title":"Breast"},{"issue":"2","key":"pone.0339543.ref038","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1093\/annonc\/mdt496","article-title":"Gene expression profiles of inflammatory breast cancer: correlation with response to neoadjuvant chemotherapy and metastasis-free survival","volume":"25","author":"F Bertucci","year":"2014","journal-title":"Ann Oncol"},{"issue":"9","key":"pone.0339543.ref039","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0222336","article-title":"Comparison of molecular profile in triple-negative inflammatory and non-inflammatory breast cancer not of mesenchymal stem-like subtype","volume":"14","author":"Y Funakoshi","year":"2019","journal-title":"PLoS One"},{"issue":"3","key":"pone.0339543.ref040","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1007\/s10549-013-2501-6","article-title":"Genomic and expression analysis of microdissected inflammatory breast cancer","volume":"138","author":"WA Woodward","year":"2013","journal-title":"Breast Cancer Res Treat"},{"key":"pone.0339543.ref041","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gku476","article-title":"LINCS Canvas Browser: interactive web app to query, browse and interrogate LINCS L1000 gene expression signatures","volume":"42","author":"Q Duan","year":"2014","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"pone.0339543.ref042","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/j.cell.2017.10.049","article-title":"A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles","volume":"171","author":"A Subramanian","year":"2017","journal-title":"Cell"},{"issue":"6","key":"pone.0339543.ref043","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1177\/1087057108318428","article-title":"Application of a high-content multiparameter cytotoxicity assay to prioritize compounds based on toxicity potential in humans","volume":"13","author":"VC Abraham","year":"2008","journal-title":"J Biomol Screen"},{"key":"pone.0339543.ref044","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.canlet.2017.09.033","article-title":"Pharmacological targeting of GLI1 inhibits proliferation, tumor emboli formation and in vivo tumor growth of inflammatory breast cancer cells","volume":"411","author":"HO Oladapo","year":"2017","journal-title":"Cancer letters"},{"issue":"1","key":"pone.0339543.ref045","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.canlet.2013.05.017","article-title":"Quantitative high-throughput efficacy profiling of approved oncology drugs in inflammatory breast cancer models of acquired drug resistance and re-sensitization","volume":"337","author":"KP Williams","year":"2013","journal-title":"Cancer Lett"},{"issue":"1","key":"pone.0339543.ref046","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/s41597-019-0255-7","article-title":"A high-throughput drug combination screen of targeted small molecule inhibitors in cancer cell lines","volume":"6","author":"\u00c5 Flobak","year":"2019","journal-title":"Sci Data"},{"issue":"12","key":"pone.0339543.ref047","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1038\/s42256-019-0122-4","article-title":"Prediction of drug combination effects with a minimal set of experiments","volume":"1","author":"A Ianevski","year":"2019","journal-title":"Nat Mach Intell"},{"key":"pone.0339543.ref048","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.coph.2018.07.008","article-title":"Recent advances in combinatorial drug screening and synergy scoring","volume":"42","author":"T Pemovska","year":"2018","journal-title":"Curr Opin Pharmacol"},{"key":"pone.0339543.ref049","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkac382","article-title":"SynergyFinder 3.0: an interactive analysis and consensus interpretation of multi-drug synergies across multiple samples","volume":"50","author":"A Ianevski","year":"2022","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"pone.0339543.ref050","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.gpb.2022.01.004","article-title":"SynergyFinder Plus: Toward Better Interpretation and Annotation of Drug Combination Screening Datasets","volume":"20","author":"S Zheng","year":"2022","journal-title":"Genomics Proteomics Bioinformatics"},{"issue":"5","key":"pone.0339543.ref051","article-title":"A simple high-content cell cycle assay reveals frequent discrepancies between cell number and ATP and MTS proliferation assays","volume":"8","author":"GKY Chan","year":"2013","journal-title":"PLoS One"},{"issue":"9","key":"pone.0339543.ref052","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.1158\/1535-7163.MCT-06-0452","article-title":"The farnesyltransferase inhibitor R115777 (tipifarnib) in combination with tamoxifen acts synergistically to inhibit MCF-7 breast cancer cell proliferation and cell cycle progression in vitro and in vivo","volume":"6","author":"L-A Martin","year":"2007","journal-title":"Mol Cancer Ther"},{"issue":"8","key":"pone.0339543.ref053","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1002\/ar.20938","article-title":"Gefitinib inhibits the proliferation of pancreatic cancer cells via cell cycle arrest","volume":"292","author":"X Zhou","year":"2009","journal-title":"Anat Rec (Hoboken)"},{"issue":"8","key":"pone.0339543.ref054","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1038\/sj.bjc.6695007","article-title":"Molecular cytogenetic analysis of 11 new breast cancer cell lines","volume":"81","author":"F Forozan","year":"1999","journal-title":"Br J Cancer"},{"issue":"1","key":"pone.0339543.ref055","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41523-024-00664-0","article-title":"Altered ribosomal profile in acquired resistance and reversal associates with pathological response to chemotherapy in inflammatory breast cancer","volume":"10","author":"GR Devi","year":"2024","journal-title":"NPJ Breast Cancer"},{"issue":"1","key":"pone.0339543.ref056","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1475-2867-5-11","article-title":"In vitro analysis of the invasive phenotype of SUM 149, an inflammatory breast cancer cell line","volume":"5","author":"MR Hoffmeyer","year":"2005","journal-title":"Cancer Cell Int"},{"issue":"8","key":"pone.0339543.ref057","first-page":"575","article-title":"Reversion of RhoC GTPase-induced inflammatory breast cancer phenotype by treatment with a farnesyl transferase inhibitor","volume":"1","author":"KL van Golen","year":"2002","journal-title":"Mol Cancer Ther"},{"issue":"1","key":"pone.0339543.ref058","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s11060-023-04526-w","article-title":"Combination drug screen identifies synergistic drug interaction of BCL-XL and class I histone deacetylase inhibitors in MYC-amplified medulloblastoma cells","volume":"166","author":"S Zeuner","year":"2024","journal-title":"J Neurooncol"},{"key":"pone.0339543.ref059","volume-title":"IBC treatment algorithm","author":"MD Anderson","year":"2023"},{"issue":"5","key":"pone.0339543.ref060","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1007\/s10787-020-00711-9","article-title":"Lapatinib inhibits doxorubicin induced migration of HER2-positive breast cancer cells","volume":"28","author":"N Chintalaramulu","year":"2020","journal-title":"Inflammopharmacology"},{"issue":"9","key":"pone.0339543.ref061","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1200\/JCO.2014.58.1967","article-title":"Tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2-positive and triple-negative primary breast cancers","volume":"33","author":"C Denkert","year":"2015","journal-title":"J Clin Oncol"},{"key":"pone.0339543.ref062","doi-asserted-by":"crossref","first-page":"100110","DOI":"10.1016\/j.crphar.2022.100110","article-title":"Evaluation of synergism in drug combinations and reference models for future orientations in oncology","volume":"3","author":"D Duarte","year":"2022","journal-title":"Curr Res Pharmacol Drug Discov"},{"key":"pone.0339543.ref063","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.3389\/fphar.2019.01384","article-title":"Additive Dose Response Models: Defining Synergy","volume":"10","author":"S Lederer","year":"2019","journal-title":"Front Pharmacol"},{"key":"pone.0339543.ref064","doi-asserted-by":"crossref","first-page":"158","DOI":"10.3389\/fphar.2017.00158","article-title":"An Introduction to Terminology and Methodology of Chemical Synergy-Perspectives from Across Disciplines","volume":"8","author":"KR Roell","year":"2017","journal-title":"Front Pharmacol"},{"issue":"5","key":"pone.0339543.ref065","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1006752","article-title":"Drug combination sensitivity scoring facilitates the discovery of synergistic and efficacious drug combinations in cancer","volume":"15","author":"A Malyutina","year":"2019","journal-title":"PLoS Comput Biol"},{"issue":"8","key":"pone.0339543.ref066","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1177\/2472555220924478","article-title":"Identification of a Triple Drug Combination That Is Synergistically Cytotoxic for Triple-Negative Breast Cancer Cells Using a Novel Combination Discovery Approach","volume":"25","author":"S Ahmad","year":"2020","journal-title":"SLAS Discov"},{"issue":"3","key":"pone.0339543.ref067","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1093\/carcin\/bgx003","article-title":"Bisphenol A activates EGFR and ERK promoting proliferation, tumor spheroid formation and resistance to EGFR pathway inhibition in estrogen receptor-negative inflammatory breast cancer cells","volume":"38","author":"SJ Sauer","year":"2017","journal-title":"Carcinogenesis"},{"issue":"18","key":"pone.0339543.ref068","doi-asserted-by":"crossref","first-page":"5639","DOI":"10.1021\/jm050392q","article-title":"Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitumor activity","volume":"48","author":"M Wittman","year":"2005","journal-title":"J Med Chem"},{"issue":"17","key":"pone.0339543.ref069","first-page":"3859","article-title":"Tyrphostin AG 1478 preferentially inhibits human glioma cells expressing truncated rather than wild-type epidermal growth factor receptors","volume":"56","author":"Y Han","year":"1996","journal-title":"Cancer Res"},{"issue":"5205","key":"pone.0339543.ref070","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1126\/science.7892601","article-title":"Tyrosine kinase inhibition: an approach to drug development","volume":"267","author":"A Levitzki","year":"1995","journal-title":"Science"},{"issue":"6","key":"pone.0339543.ref071","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S1535-6108(03)00303-9","article-title":"A chemical genetic screen identifies inhibitors of regulated nuclear export of a Forkhead transcription factor in PTEN-deficient tumor cells","volume":"4","author":"TR Kau","year":"2003","journal-title":"Cancer Cell"},{"issue":"4","key":"pone.0339543.ref072","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/S1470-2045(00)00135-2","article-title":"CCI-779: a new targeted anticancer agent","volume":"1","author":"E Hutchinson","year":"2000","journal-title":"The Lancet Oncology"},{"issue":"10","key":"pone.0339543.ref073","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1007\/s11912-019-0842-y","article-title":"Inflammatory Breast Cancer: a Separate Entity","volume":"21","author":"JM Rosenbluth","year":"2019","journal-title":"Curr Oncol Rep"},{"key":"pone.0339543.ref074","doi-asserted-by":"crossref","first-page":"1352803","DOI":"10.3389\/fmed.2024.1352803","article-title":"Drug repurposing for rare: progress and opportunities for the rare disease community","volume":"11","author":"AH Jonker","year":"2024","journal-title":"Front Med (Lausanne)"},{"key":"pone.0339543.ref075","doi-asserted-by":"crossref","first-page":"324","DOI":"10.7150\/jca.2.324","article-title":"Targeting EGFR in Triple Negative Breast Cancer","volume":"2","author":"NT Ueno","year":"2011","journal-title":"J Cancer"},{"key":"pone.0339543.ref076","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1186\/1471-2164-13-619","article-title":"Molecular characterisation of cell line models for triple-negative breast cancers","volume":"13","author":"A Grigoriadis","year":"2012","journal-title":"BMC Genomics"},{"issue":"1","key":"pone.0339543.ref077","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s13058-015-0549-4","article-title":"Mesenchymal stem cells mediate the clinical phenotype of inflammatory breast cancer in a preclinical model","volume":"17","author":"L Lacerda","year":"2015","journal-title":"Breast Cancer Res"},{"issue":"20","key":"pone.0339543.ref078","doi-asserted-by":"crossref","first-page":"3248","DOI":"10.1200\/JCO.2009.21.8594","article-title":"Phase II study to evaluate the efficacy and safety of neoadjuvant lapatinib plus paclitaxel in patients with inflammatory breast cancer","volume":"28","author":"H Boussen","year":"2010","journal-title":"J Clin Oncol"},{"issue":"6","key":"pone.0339543.ref079","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/S1470-2045(09)70087-7","article-title":"Lapatinib monotherapy in patients with HER2-overexpressing relapsed or refractory inflammatory breast cancer: final results and survival of the expanded HER2+ cohort in EGF103009, a phase II study","volume":"10","author":"B Kaufman","year":"2009","journal-title":"Lancet Oncol"},{"key":"pone.0339543.ref080","doi-asserted-by":"crossref","unstructured":"Alvarez RH, Cristofanilli M, Ensor J, Lucci A, Yang WT, Le-Petross HT, et al. Limited efficacy and significant toxicities of lapatinib (Lap) plus chemotherapy as neoadjuvant therapy (NAC) for HER2-positive inflammatory breast cancer (IBC) patients (Pts). In: American Society of Clinical Oncology, 2012.","DOI":"10.1200\/jco.2012.30.15_suppl.594"},{"key":"pone.0339543.ref081","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2147\/ODRR.S35339","article-title":"Tipifarnib and farnesyltransferase inhibitors in the treatment of inflammatory breast cancer: is the story over? A review","author":"L Usha","year":"2013","journal-title":"ODRR"},{"key":"pone.0339543.ref082","doi-asserted-by":"crossref","first-page":"39190","DOI":"10.1038\/srep39190","article-title":"Macrophages Enhance Migration in Inflammatory Breast Cancer Cells via RhoC GTPase Signaling","volume":"6","author":"SG Allen","year":"2016","journal-title":"Sci Rep"},{"issue":"12","key":"pone.0339543.ref083","doi-asserted-by":"crossref","first-page":"3717","DOI":"10.3390\/cancers12123717","article-title":"Differential Effects of IGF-1R Small Molecule Tyrosine Kinase Inhibitors BMS-754807 and OSI-906 on Human Cancer Cell Lines","volume":"12","author":"M Fuentes-Baile","year":"2020","journal-title":"Cancers (Basel)"},{"issue":"1","key":"pone.0339543.ref084","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1158\/1078-0432.CCR-08-0801","article-title":"BMS-536924 reverses IGF-IR-induced transformation of mammary epithelial cells and causes growth inhibition and polarization of MCF7 cells","volume":"15","author":"BC Litzenburger","year":"2009","journal-title":"Clin Cancer Res"},{"issue":"24","key":"pone.0339543.ref085","doi-asserted-by":"crossref","first-page":"10238","DOI":"10.1158\/0008-5472.CAN-08-2755","article-title":"Phosphorylated insulin-like growth factor-i\/insulin receptor is present in all breast cancer subtypes and is related to poor survival","volume":"68","author":"JH Law","year":"2008","journal-title":"Cancer Res"},{"issue":"6","key":"pone.0339543.ref086","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1530\/ERC-11-0136","article-title":"IGF1\/insulin receptor kinase inhibition by BMS-536924 is better tolerated than alloxan-induced hypoinsulinemia and more effective than metformin in the treatment of experimental insulin-responsive breast cancer","volume":"18","author":"CJ Dool","year":"2011","journal-title":"Endocr Relat Cancer"},{"issue":"1","key":"pone.0339543.ref087","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.gendis.2022.03.002","article-title":"Drugging IGF-1R in cancer: New insights and emerging opportunities","volume":"10","author":"P Wang","year":"2022","journal-title":"Genes Dis"},{"key":"pone.0339543.ref088","doi-asserted-by":"crossref","first-page":"155620","DOI":"10.1016\/j.prp.2024.155620","article-title":"Recent update on IGF-1\/IGF-1R signaling axis as a promising therapeutic target for triple-negative breast cancer","volume":"263","author":"S Kumar","year":"2024","journal-title":"Pathol Res Pract"},{"issue":"2","key":"pone.0339543.ref089","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s10549-011-1910-7","article-title":"Phase II trial of temsirolimus in patients with metastatic breast cancer","volume":"136","author":"GF Fleming","year":"2012","journal-title":"Breast Cancer Res Treat"},{"issue":"6","key":"pone.0339543.ref090","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1056\/NEJMoa1109653","article-title":"Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer","volume":"366","author":"J Baselga","year":"2012","journal-title":"N Engl J Med"},{"key":"pone.0339543.ref091","doi-asserted-by":"crossref","first-page":"73","DOI":"10.4137\/BCBCR.S29268","article-title":"Everolimus in the Treatment of Metastatic Breast Cancer","volume":"9","author":"ME Royce","year":"2015","journal-title":"Breast Cancer (Auckl)"},{"issue":"2","key":"pone.0339543.ref092","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1021\/cb500856c","article-title":"Anticancer\/antiviral agent Akt inhibitor-IV massively accumulates in mitochondria and potently disrupts cellular bioenergetics","volume":"10","author":"JM Meinig","year":"2015","journal-title":"ACS Chem Biol"},{"issue":"4","key":"pone.0339543.ref093","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.slasd.2023.04.004","article-title":"High-throughput approaches to uncover synergistic drug combinations in leukemia","volume":"28","author":"EJ Chory","year":"2023","journal-title":"SLAS Discov"},{"issue":"2","key":"pone.0339543.ref094","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1080\/19466315.2018.1437071","article-title":"Evaluation of drug combination effect using a Bliss independence dose-response surface model","volume":"10","author":"Q Liu","year":"2018","journal-title":"Stat Biopharm Res"},{"issue":"6","key":"pone.0339543.ref095","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/s41573-026-01388-5","article-title":"A renaissance in targeting the PI3K\/AKT\/mTOR pathway","volume":"25","author":"SE Conduit","year":"2026","journal-title":"Nat Rev Drug Discov"},{"issue":"1","key":"pone.0339543.ref096","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s12943-023-01827-6","article-title":"PI3K\/AKT\/mTOR signaling transduction pathway and targeted therapies in cancer","volume":"22","author":"A Glaviano","year":"2023","journal-title":"Mol Cancer"},{"issue":"1","key":"pone.0339543.ref097","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/s41392-021-00828-5","article-title":"Targeting PI3K\/Akt signal transduction for cancer therapy","volume":"6","author":"Y He","year":"2021","journal-title":"Signal Transduct Target Ther"},{"issue":"16","key":"pone.0339543.ref098","doi-asserted-by":"crossref","first-page":"3949","DOI":"10.3390\/cancers13163949","article-title":"The Pathogenic Role of PI3K\/AKT Pathway in Cancer Onset and Drug Resistance: An Updated Review","volume":"13","author":"F Rascio","year":"2021","journal-title":"Cancers (Basel)"},{"issue":"1","key":"pone.0339543.ref099","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1158\/0008-5472.CAN-08-0835","article-title":"The mechanisms of differential sensitivity to an insulin-like growth factor-1 receptor inhibitor (BMS-536924) and rationale for combining with EGFR\/HER2 inhibitors","volume":"69","author":"F Huang","year":"2009","journal-title":"Cancer Res"},{"issue":"21","key":"pone.0339543.ref100","doi-asserted-by":"crossref","first-page":"6639","DOI":"10.1158\/1078-0432.CCR-09-0951","article-title":"Epidermal growth factor receptor tyrosine kinase inhibitor reverses mesenchymal to epithelial phenotype and inhibits metastasis in inflammatory breast cancer","volume":"15","author":"D Zhang","year":"2009","journal-title":"Clin Cancer Res"},{"issue":"49","key":"pone.0339543.ref101","doi-asserted-by":"crossref","first-page":"37728","DOI":"10.1074\/jbc.M606532200","article-title":"Autocrine and juxtacrine effects of amphiregulin on the proliferative, invasive, and migratory properties of normal and neoplastic human mammary epithelial cells","volume":"281","author":"NE Willmarth","year":"2006","journal-title":"J Biol Chem"},{"issue":"1","key":"pone.0339543.ref102","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13045-020-00904-3","article-title":"Insulin-like growth factor receptor signaling in tumorigenesis and drug resistance: a challenge for cancer therapy","volume":"13","author":"H Hua","year":"2020","journal-title":"J Hematol Oncol"},{"issue":"6","key":"pone.0339543.ref103","doi-asserted-by":"crossref","first-page":"342","DOI":"10.5483\/BMBRep.2015.48.6.157","article-title":"Insulin activates EGFR by stimulating its interaction with IGF-1R in low-EGFR-expressing TNBC cells","volume":"48","author":"M Shin","year":"2015","journal-title":"BMB Rep"},{"issue":"9","key":"pone.0339543.ref104","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.1158\/1535-7163.MCT-08-0493","article-title":"HER receptor signaling confers resistance to the insulin-like growth factor-I receptor inhibitor, BMS-536924","volume":"7","author":"P Haluska","year":"2008","journal-title":"Mol Cancer Ther"},{"issue":"1","key":"pone.0339543.ref105","doi-asserted-by":"crossref","first-page":"4607","DOI":"10.1038\/s41467-020-18442-4","article-title":"Transient IGF-1R inhibition combined with osimertinib eradicates AXL-low expressing EGFR mutated lung cancer","volume":"11","author":"R Wang","year":"2020","journal-title":"Nat Commun"},{"issue":"5","key":"pone.0339543.ref106","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/s11523-017-0514-5","article-title":"Insulin-Like Growth Factor (IGF) Pathway Targeting in Cancer: Role of the IGF Axis and Opportunities for Future Combination Studies","volume":"12","author":"A Simpson","year":"2017","journal-title":"Target Oncol"},{"issue":"17","key":"pone.0339543.ref107","doi-asserted-by":"crossref","first-page":"8665","DOI":"10.3390\/ijms26178665","article-title":"Targeting EGFR\/IGF-IR Functional Crosstalk in 2D and 3D Triple-Negative Breast Cancer Models to Evaluate Tumor Progression","volume":"26","author":"S Kremmydas","year":"2025","journal-title":"Int J Mol Sci"},{"issue":"1","key":"pone.0339543.ref108","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s12929-022-00860-9","article-title":"Akt: a key transducer in cancer","volume":"29","author":"P-J Tsai","year":"2022","journal-title":"J Biomed Sci"},{"issue":"5","key":"pone.0339543.ref109","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.cellsig.2009.01.004","article-title":"Akt-dependent and -independent mechanisms of mTOR regulation in cancer","volume":"21","author":"RM Memmott","year":"2009","journal-title":"Cell Signal"},{"issue":"1","key":"pone.0339543.ref110","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/s41392-023-01608-z","article-title":"Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease","volume":"8","author":"V Panwar","year":"2023","journal-title":"Signal Transduct Target Ther"},{"issue":"1","key":"pone.0339543.ref111","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0054918","article-title":"A comparison of Ku0063794, a dual mTORC1 and mTORC2 inhibitor, and temsirolimus in preclinical renal cell carcinoma models","volume":"8","author":"H Zhang","year":"2013","journal-title":"PLoS One"},{"issue":"34","key":"pone.0339543.ref112","doi-asserted-by":"crossref","first-page":"4103","DOI":"10.1200\/JCO.24.00427","article-title":"FDA Approval Summary: Capivasertib with Fulvestrant for HR-positive, HER2-negative Locally Advanced or Metastatic Breast Cancer with PIK3CA\/AKT1\/PTEN Alterations","volume":"42","author":"A Dilawari","year":"2024","journal-title":"Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology"},{"issue":"8","key":"pone.0339543.ref113","doi-asserted-by":"crossref","first-page":"6052","DOI":"10.1021\/acs.jmedchem.4c00075","article-title":"Akt Inhibitor Advancements: From Capivasertib Approval to Covalent-Allosteric Promises","volume":"67","author":"KA Pervanidis","year":"2024","journal-title":"J Med Chem"},{"issue":"3","key":"pone.0339543.ref114","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s40265-024-01998-6","article-title":"Capivasertib: first approval","volume":"84","author":"MS Capivasertib","year":"2024","journal-title":"Drugs"},{"issue":"20","key":"pone.0339543.ref115","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1056\/NEJMoa1813904","article-title":"Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer","volume":"380","author":"F Andr\u00e9","year":"2019","journal-title":"N Engl J Med"},{"issue":"2","key":"pone.0339543.ref116","doi-asserted-by":"crossref","first-page":"105936","DOI":"10.1016\/j.esmoop.2025.105936","article-title":"Clinical management of common toxicities with inhibitors targeting the PI3K\/AKT\/mTOR pathway in breast cancer","volume":"11","author":"KL Jhaveri","year":"2026","journal-title":"ESMO Open"},{"issue":"12","key":"pone.0339543.ref117","article-title":"Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4\/6 inhibitor (BYLieve): one cohort of a phase 2, multicentre, open-label, non-comparative study","volume":"25","author":"HS Rugo","year":"2024","journal-title":"Lancet Oncol"},{"key":"pone.0339543.ref118","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41523-020-0173-z","article-title":"Development and implementation of the SUM breast cancer cell line functional genomics knowledge base","volume":"6","author":"SP Ethier","year":"2020","journal-title":"NPJ Breast Cancer"},{"issue":"19","key":"pone.0339543.ref119","doi-asserted-by":"crossref","first-page":"13021","DOI":"10.1074\/jbc.M709698200","article-title":"Mammalian target of rapamycin contributes to the acquired apoptotic resistance of human mesothelioma multicellular spheroids","volume":"283","author":"D Barbone","year":"2008","journal-title":"J Biol Chem"},{"issue":"10","key":"pone.0339543.ref120","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1158\/1541-7786.MCR-12-0173","article-title":"Regulation of inflammatory breast cancer cell invasion through Akt1\/PKB\u03b1 phosphorylation of RhoC GTPase","volume":"10","author":"HL Lehman","year":"2012","journal-title":"Mol Cancer Res"},{"issue":"1","key":"pone.0339543.ref121","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1186\/s12885-017-3695-5","article-title":"Inhibition of PI3K\/Akt\/mTOR overcomes cisplatin resistance in the triple negative breast cancer cell line HCC38","volume":"17","author":"K Gohr","year":"2017","journal-title":"BMC Cancer"},{"issue":"11","key":"pone.0339543.ref122","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.3390\/cancers14112807","article-title":"SCAMP3 Regulates EGFR and Promotes Proliferation and Migration of Triple-Negative Breast Cancer Cells through the Modulation of AKT, ERK, and STAT3 Signaling Pathways","volume":"14","author":"A Acevedo-D\u00edaz","year":"2022","journal-title":"Cancers (Basel)"},{"issue":"3","key":"pone.0339543.ref123","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.molcel.2010.02.031","article-title":"The actin-bundling protein palladin is an Akt1-specific substrate that regulates breast cancer cell migration","volume":"38","author":"YR Chin","year":"2010","journal-title":"Mol Cell"},{"issue":"1","key":"pone.0339543.ref124","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s13058-017-0868-8","article-title":"Two distinct mTORC2-dependent pathways converge on Rac1 to drive breast cancer metastasis","volume":"19","author":"M Morrison Joly","year":"2017","journal-title":"Breast Cancer Res"},{"issue":"1","key":"pone.0339543.ref125","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1186\/s13046-023-02850-7","article-title":"IGF-1R targeting in cancer - does sub-cellular localization matter?","volume":"42","author":"UK Soni","year":"2023","journal-title":"J Exp Clin Cancer Res"},{"issue":"3","key":"pone.0339543.ref126","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1158\/0008-5472.CAN-05-2925","article-title":"mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt","volume":"66","author":"KE O\u2019Reilly","year":"2006","journal-title":"Cancer Res"},{"issue":"2","key":"pone.0339543.ref127","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0117745","article-title":"Upregulation of IGF-1R expression during neoadjuvant therapy predicts poor outcome in breast cancer patients","volume":"10","author":"S Heskamp","year":"2015","journal-title":"PLoS One"},{"issue":"10","key":"pone.0339543.ref128","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1038\/s41419-018-1025-8","article-title":"IGF1R upregulation confers resistance to isoform-specific inhibitors of PI3K in PIK3CA-driven ovarian cancer","volume":"9","author":"J Zorea","year":"2018","journal-title":"Cell Death Dis"},{"issue":"1","key":"pone.0339543.ref129","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.ccr.2010.10.031","article-title":"AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity","volume":"19","author":"S Chandarlapaty","year":"2011","journal-title":"Cancer Cell"},{"issue":"11","key":"pone.0339543.ref130","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1002\/psp4.12107","article-title":"Systematic Quality Control Analysis of LINCS Data","volume":"5","author":"L Cheng","year":"2016","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"issue":"40","key":"pone.0339543.ref131","doi-asserted-by":"crossref","first-page":"67904","DOI":"10.18632\/oncotarget.18958","article-title":"EGFR signaling promotes inflammation and cancer stem-like activity in inflammatory breast cancer","volume":"8","author":"X Wang","year":"2017","journal-title":"Oncotarget"},{"issue":"1","key":"pone.0339543.ref132","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13000-021-01174-4","article-title":"RRM2 expression in different molecular subtypes of breast cancer and its prognostic significance","volume":"17","author":"MA Abdel-Rahman","year":"2022","journal-title":"Diagn Pathol"},{"issue":"1","key":"pone.0339543.ref133","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.gendis.2022.11.022","article-title":"Ribonucleotide reductase M2 (RRM2): Regulation, function and targeting strategy in human cancer","volume":"11","author":"Z Zuo","year":"2022","journal-title":"Genes Dis"},{"issue":"8","key":"pone.0339543.ref134","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1158\/0008-5472.CAN-20-2860","article-title":"Targeting IGF Perturbs Global Replication through Ribonucleotide Reductase Dysfunction","volume":"81","author":"G Rieunier","year":"2021","journal-title":"Cancer Res"},{"issue":"10","key":"pone.0339543.ref135","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1096\/fasebj.9.10.7615158","article-title":"Regulation of the tissue factor gene","volume":"9","author":"N Mackman","year":"1995","journal-title":"FASEB J"},{"issue":"1","key":"pone.0339543.ref136","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s13045-020-00932-z","article-title":"Beyond thrombosis: the impact of tissue factor signaling in cancer","volume":"13","author":"D Unruh","year":"2020","journal-title":"J Hematol Oncol"},{"issue":"1","key":"pone.0339543.ref137","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s40364-023-00504-6","article-title":"Tissue factor (coagulation factor III): a potential double-edge molecule to be targeted and re-targeted toward cancer","volume":"11","author":"SE Ahmadi","year":"2023","journal-title":"Biomark Res"},{"issue":"3","key":"pone.0339543.ref138","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1002\/ijc.28959","article-title":"The role of tissue factor isoforms in cancer biology","volume":"137","author":"U Leppert","year":"2015","journal-title":"Int J Cancer"},{"issue":"19","key":"pone.0339543.ref139","doi-asserted-by":"crossref","first-page":"4883","DOI":"10.3390\/cancers15194883","article-title":"Influence of Macrophages on Vascular Invasion of Inflammatory Breast Cancer Emboli Measured Using an In Vitro Microfluidic Multi-Cellular Platform","volume":"15","author":"M Gadde","year":"2023","journal-title":"Cancers (Basel)"},{"key":"pone.0339543.ref140","doi-asserted-by":"crossref","DOI":"10.21037\/tcr.2019.03.24","article-title":"Pathological and molecular characteristics of inflammatory breast cancer","volume":"8","author":"M Di Bonito","year":"2019","journal-title":"Transl Cancer Res"},{"issue":"5845","key":"pone.0339543.ref141","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1126\/science.1147939","article-title":"UHRF1 plays a role in maintaining DNA methylation in mammalian cells","volume":"317","author":"M Bostick","year":"2007","journal-title":"Science"},{"issue":"31","key":"pone.0339543.ref142","doi-asserted-by":"crossref","first-page":"51946","DOI":"10.18632\/oncotarget.17393","article-title":"The epigenetic integrator UHRF1: on the road to become a universal biomarker for cancer","volume":"8","author":"W Ashraf","year":"2017","journal-title":"Oncotarget"},{"issue":"1","key":"pone.0339543.ref143","doi-asserted-by":"crossref","first-page":"18371","DOI":"10.1038\/s41598-024-69110-2","article-title":"Identification of differentially expressed tumour-related genes regulated by UHRF1-driven DNA methylation","volume":"14","author":"Q Dong","year":"2024","journal-title":"Sci Rep"},{"issue":"5","key":"pone.0339543.ref144","doi-asserted-by":"crossref","DOI":"10.1530\/ERC-19-0501","article-title":"Cyclin E1 and cyclin E2 in ER+ breast cancer: prospects as biomarkers and therapeutic targets","volume":"27","author":"HH Milioli","year":"2020","journal-title":"Endocr Relat Cancer"},{"issue":"9","key":"pone.0339543.ref145","doi-asserted-by":"crossref","first-page":"14897","DOI":"10.18632\/oncotarget.14689","article-title":"Cyclin E overexpression as a biomarker for combination treatment strategies in inflammatory breast cancer","volume":"8","author":"A Alexander","year":"2017","journal-title":"Oncotarget"},{"issue":"2","key":"pone.0339543.ref146","doi-asserted-by":"crossref","first-page":"100868","DOI":"10.1016\/j.isci.2020.100868","article-title":"Comprehensive Proteomic Characterization Reveals Subclass-Specific Molecular Aberrations within Triple-negative Breast Cancer","volume":"23","author":"M Kosok","year":"2020","journal-title":"iScience"},{"issue":"6","key":"pone.0339543.ref147","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1002\/jso.24705","article-title":"Caspase14 expression is associated with triple negative phenotypes and cancer stem cell marker expression in breast cancer patients","volume":"116","author":"T Handa","year":"2017","journal-title":"J Surg Oncol"},{"issue":"10","key":"pone.0339543.ref148","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1038\/sj.cdd.4400444","article-title":"Identification of a new caspase homologue: caspase-14","volume":"5","author":"M Van de Craen","year":"1998","journal-title":"Cell Death & Differentiation"},{"issue":"26","key":"pone.0339543.ref149","doi-asserted-by":"crossref","first-page":"6619","DOI":"10.1182\/blood-2009-01-199588","article-title":"KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells","volume":"113","author":"SM Henson","year":"2009","journal-title":"Blood"},{"issue":"1","key":"pone.0339543.ref150","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1182\/blood-2003-12-4295","article-title":"GILZ, a new target for the transcription factor FoxO3, protects T lymphocytes from interleukin-2 withdrawal-induced apoptosis","volume":"104","author":"M-L Asselin-Labat","year":"2004","journal-title":"Blood"},{"key":"pone.0339543.ref151","doi-asserted-by":"crossref","first-page":"308","DOI":"10.3389\/fphar.2019.00308","article-title":"Glucocorticoid-Induced Leucine Zipper: A Novel Anti-inflammatory Molecule","volume":"10","author":"O Bereshchenko","year":"2019","journal-title":"Front Pharmacol"},{"key":"pone.0339543.ref152","doi-asserted-by":"crossref","first-page":"1078051","DOI":"10.3389\/fonc.2022.1078051","article-title":"FOXO3 gene hypermethylation and its marked downregulation in breast cancer cases: A study on female patients","volume":"12","author":"Sadaf","year":"2023","journal-title":"Front Oncol"},{"issue":"11","key":"pone.0339543.ref153","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1038\/onc.2011.328","article-title":"GILZ inhibits the mTORC2\/AKT pathway in BCR-ABL(+) cells","volume":"31","author":"S Joha","year":"2012","journal-title":"Oncogene"},{"issue":"8","key":"pone.0339543.ref154","doi-asserted-by":"crossref","first-page":"107451","DOI":"10.1016\/j.isci.2023.107451","article-title":"TSC22D3 as an immune-related prognostic biomarker for acute myeloid leukemia","volume":"26","author":"Y Li","year":"2023","journal-title":"iScience"},{"key":"pone.0339543.ref155","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.jsbmb.2007.11.003","article-title":"Dual regulation of glucocorticoid-induced leucine zipper (GILZ) by the glucocorticoid receptor and the PI3-kinase\/AKT pathways in multiple myeloma","volume":"110","author":"KD Grugan","year":"2008","journal-title":"J Steroid Biochem Mol Biol"},{"issue":"6","key":"pone.0339543.ref156","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.ccr.2006.10.008","article-title":"A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes","volume":"10","author":"RM Neve","year":"2006","journal-title":"Cancer Cell"},{"key":"pone.0339543.ref157","doi-asserted-by":"crossref","first-page":"129","DOI":"10.14740\/wjon1161","article-title":"Inflammatory Breast Cancer: A Literature Review","volume":"9","author":"F Mamouch","year":"2018","journal-title":"World J Oncol"},{"issue":"7","key":"pone.0339543.ref158","doi-asserted-by":"crossref","first-page":"12417","DOI":"10.18632\/oncotarget.13778","article-title":"Developmental therapeutics for inflammatory breast cancer: Biology and translational directions","volume":"8","author":"R Costa","year":"2017","journal-title":"Oncotarget"},{"issue":"2","key":"pone.0339543.ref159","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1124\/mol.114.095380","article-title":"Insulin-like growth factor-1 receptor signaling increases the invasive potential of human epidermal growth factor receptor 2-overexpressing breast cancer cells via Src-focal adhesion kinase and forkhead box protein M1","volume":"87","author":"E Sanabria-Figueroa","year":"2015","journal-title":"Mol Pharmacol"},{"issue":"24","key":"pone.0339543.ref160","doi-asserted-by":"crossref","first-page":"36138","DOI":"10.18632\/oncotarget.9147","article-title":"Functional oncogene signatures guide rationally designed combination therapies to synergistically induce breast cancer cell death","volume":"7","author":"ST Guest","year":"2016","journal-title":"Oncotarget"},{"issue":"12","key":"pone.0339543.ref161","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1158\/1535-7163.MCT-15-0096","article-title":"Antitumor Activity of KW-2450 against Triple-Negative Breast Cancer by Inhibiting Aurora A and B Kinases","volume":"14","author":"K Kai","year":"2015","journal-title":"Mol Cancer Ther"},{"issue":"8","key":"pone.0339543.ref162","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1139\/y2012-023","article-title":"The EGFR tyrosine kinase inhibitor tyrphostin AG-1478 causes hypomagnesemia and cardiac dysfunction","volume":"90","author":"WB Weglicki","year":"2012","journal-title":"Can J Physiol Pharmacol"},{"issue":"10","key":"pone.0339543.ref163","doi-asserted-by":"crossref","first-page":"5557","DOI":"10.3390\/ijms23105557","article-title":"AG1478 Elicits a Novel Anti-Influenza Function via an EGFR-Independent, GBF1-Dependent Pathway","volume":"23","author":"X Zhou","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"10","key":"pone.0339543.ref164","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1016\/j.bcp.2006.01.020","article-title":"Preclinical analysis of the analinoquinazoline AG1478, a specific small molecule inhibitor of EGF receptor tyrosine kinase","volume":"71","author":"AG Ellis","year":"2006","journal-title":"Biochem Pharmacol"},{"issue":"1","key":"pone.0339543.ref165","article-title":"Anti-insulin-like growth factor therapy in breast cancer","volume":"61","author":"D Yee","year":"2018","journal-title":"J Mol Endocrinol"},{"key":"pone.0339543.ref166","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/s41698-017-0017-y","article-title":"Revisiting the IGF-1R as a breast cancer target","volume":"1","author":"RC Ekyalongo","year":"2017","journal-title":"NPJ Precis Oncol"},{"issue":"4","key":"pone.0339543.ref167","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1634\/theoncologist.2009-0178","article-title":"FDA approval summary: temsirolimus as treatment for advanced renal cell carcinoma","volume":"15","author":"VE Kwitkowski","year":"2010","journal-title":"Oncologist"},{"issue":"2","key":"pone.0339543.ref168","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1056\/NEJMoa2501796","article-title":"Overall Survival with Inavolisib in PIK3CA-Mutated Advanced Breast Cancer","volume":"393","author":"KL Jhaveri","year":"2025","journal-title":"N Engl J Med"},{"issue":"22","key":"pone.0339543.ref169","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1056\/NEJMoa2214131","article-title":"Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer","volume":"388","author":"NC Turner","year":"2023","journal-title":"N Engl J Med"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0339543","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:36:19Z","timestamp":1789580179000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0339543"}},"subtitle":[],"editor":[{"given":"Divijendra Natha Reddy","family":"Sirigiri","sequence":"first","affiliation":[{"name":"BMSCE: BMS College of Engineering","place":["INDIA"]}],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":169,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0339543","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]}}}