{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:51:44Z","timestamp":1791273104957,"version":"4.1.0"},"reference-count":70,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"abstract":"<jats:p>Drug resistance significantly limits the long\u2010term effectiveness of targeted therapies in lung cancer. AXL, a receptor tyrosine kinase (RTK), is a well\u2010established driver of drug resistance in many cancers, including lung cancer. Epithelial cell adhesion molecule (EpCAM), which is commonly overexpressed in epithelial cancers, is also a critical signaling molecule. In this study, we elucidated the role of EpCAM in drug resistance and its mechanistic association with AXL. We found that soluble epithelial cell adhesion molecule (sEpCAM) expression robustly enhanced hallmark cancer phenotypes and promoted pro\u2010survival functions by upregulating AXL expression. Gene expression and pathway analyses further identified significant alterations in core cancer signaling pathways, including NF\u2010kB, STAT3, AKT, and ERK. The ectopic expression of sEpCAM concurrently upregulated endogenous EpCAM expression in the tumor environment. Functionally, sEpCAM confers broad resistance to conventional chemotherapy. Drug sensitivity assays revealed that proteasome inhibition effectively reversed the sEpCAM\u2010induced drug resistance by reducing AXL protein levels. Translational analysis of the lung cancer patient cohort data indicated that patients with aggressive disease co\u2010expressing EpCAM and AXL may be particularly amenable to proteasome\u2010based therapy. Characterization of the EpCAM\u2010AXL axis gene signature further uncovered connections to p53, integrin, and Rho GTPase signaling as well as an intriguing link to tumor immune evasion. Our findings suggest that EpCAM\u2010AXL co\u2010expression in a subset of patients with lung cancer serves as both a predictive biomarker and a promising therapeutic target to counteract treatment failure.<\/jats:p>","DOI":"10.1002\/1878-0261.70342","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:04:52Z","timestamp":1791270292000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting the\n                    <scp>EpCAM<\/scp>\n                    \u2010\n                    <scp>AXL<\/scp>\n                    axis to overcome drug resistance in lung cancer"],"prefix":"10.1002","author":[{"given":"Alexa","family":"Guerrero\u2010Alba","sequence":"first","affiliation":[{"name":"Norton Thoracic Institute St. Joseph's Hospital and Medical Center  Phoenix AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Shacker","sequence":"additional","affiliation":[{"name":"School of Medicine Creighton University, Phoenix Health Sciences Campus  AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy P.","family":"Fleming","sequence":"additional","affiliation":[{"name":"Norton Thoracic Institute St. Joseph's Hospital and Medical Center  Phoenix AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Smith","sequence":"additional","affiliation":[{"name":"Norton Thoracic Institute St. Joseph's Hospital and Medical Center  Phoenix AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross M.","family":"Bremner","sequence":"additional","affiliation":[{"name":"Norton Thoracic Institute St. Joseph's Hospital and Medical Center  Phoenix AZ USA"},{"name":"School of Medicine Creighton University, Phoenix Health Sciences Campus  AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6987-8143","authenticated-orcid":false,"given":"Narendra V.","family":"Sankpal","sequence":"additional","affiliation":[{"name":"Norton Thoracic Institute St. Joseph's Hospital and Medical Center  Phoenix AZ USA"},{"name":"School of Medicine Creighton University, Phoenix Health Sciences Campus  AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"issue":"1","key":"e_1_2_11_2_1","first-page":"10","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel RL","year":"2025","journal-title":"CA Cancer J Clin"},{"issue":"48","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"78985","DOI":"10.18632\/oncotarget.12587","article-title":"The prevalence of EGFR mutation in patients with non\u2010small cell lung cancer: a systematic review and meta\u2010analysis","volume":"7","author":"Zhang YL","year":"2016","journal-title":"Oncotarget"},{"issue":"8","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/ng.2330","article-title":"Activation of the AXL kinase causes resistance to EGFR\u2010targeted therapy in lung cancer","volume":"44","author":"Zhang Z","year":"2012","journal-title":"Nat Genet"},{"issue":"10","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1158\/2159-8290.CD-12-0108","article-title":"HER2 amplification: a potential mechanism of acquired resistance to EGFR inhibition in EGFR\u2010mutant lung cancers that lack the second\u2010site EGFRT790M mutation","volume":"2","author":"Takezawa K","year":"2012","journal-title":"Cancer Discov"},{"issue":"11","key":"e_1_2_11_6_1","doi-asserted-by":"crossref","DOI":"10.1093\/jnci\/djx065","article-title":"An ERBB1\u20103 neutralizing antibody mixture with high activity against drug\u2010resistant HER2+ breast cancers with ERBB ligand overexpression","volume":"109","author":"Schwarz LJ","year":"2017","journal-title":"J Natl Cancer Inst"},{"issue":"3","key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.15171\/apb.2017.041","article-title":"The different mechanisms of cancer drug resistance: a brief review","volume":"7","author":"Mansoori B","year":"2017","journal-title":"Adv Pharm Bull"},{"issue":"9","key":"e_1_2_11_8_1","doi-asserted-by":"crossref","DOI":"10.3390\/cells8091013","article-title":"Highlights in resistance mechanism pathways for combination therapy","volume":"8","author":"Delou JMA","year":"2019","journal-title":"Cells"},{"issue":"14","key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1158\/0008-5472.CAN-24-3841","article-title":"AXL tyrosine kinases: a growing isoform family that promotes cancer pathogenesis","volume":"85","author":"Eriksen Gjerstad M","year":"2025","journal-title":"Cancer Res"},{"issue":"14","key":"e_1_2_11_10_1","doi-asserted-by":"crossref","first-page":"3725","DOI":"10.1158\/0008-5472.CAN-17-0392","article-title":"AXL\u2010driven EMT state as a targetable conduit in cancer","volume":"77","author":"Antony J","year":"2017","journal-title":"Cancer Res"},{"issue":"7579","key":"e_1_2_11_11_1","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1038\/nature15748","article-title":"Epithelial\u2010to\u2010mesenchymal transition is not required for lung metastasis but contributes to chemoresistance","volume":"527","author":"Fischer KR","year":"2015","journal-title":"Nature"},{"issue":"1","key":"e_1_2_11_12_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s12943-024-02210-9","article-title":"AXL: shapers of tumor progression and immunosuppressive microenvironments","volume":"24","author":"Liu Y","year":"2025","journal-title":"Mol Cancer"},{"issue":"287","key":"e_1_2_11_13_1","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.2004155","article-title":"The receptor AXL diversifies EGFR signaling and limits the response to EGFR\u2010targeted inhibitors in triple\u2010negative breast cancer cells","volume":"6","author":"Meyer AS","year":"2013","journal-title":"Sci Signal"},{"issue":"1","key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/febs.16923","article-title":"The protease ADAM17 at the crossroads of disease: revisiting its significance in inflammation, cancer, and beyond","volume":"291","author":"Saad MI","year":"2024","journal-title":"FEBS J"},{"issue":"6","key":"e_1_2_11_15_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2024.107347","article-title":"Extracellular proteolysis in cancer: proteases, substrates, and mechanisms in tumor progression and metastasis","volume":"300","author":"Radisky ES","year":"2024","journal-title":"J Biol Chem"},{"issue":"18","key":"e_1_2_11_16_1","article-title":"ADAM17\u2010mediated EGFR ligand shedding directs macrophage\u2010promoted cancer cell invasion","volume":"7","author":"Gnosa SP","year":"2022","journal-title":"Insight"},{"issue":"2","key":"e_1_2_11_17_1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/ncb1824","article-title":"Nuclear signalling by tumour\u2010associated antigen EpCAM","volume":"11","author":"Maetzel D","year":"2009","journal-title":"Nat Cell Biol"},{"issue":"9","key":"e_1_2_11_18_1","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.oraloncology.2006.10.010","article-title":"Clinicopathologic significance of EpCAM expression in squamous cell carcinoma of the tongue and its possibility as a potential target for tongue cancer gene therapy","volume":"43","author":"Yanamoto S","year":"2007","journal-title":"Oral Oncol"},{"issue":"2","key":"e_1_2_11_19_1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/modpathol.3800733","article-title":"Loss of membranous ep\u2010CAM in budding colorectal carcinoma cells","volume":"20","author":"Gosens MJ","year":"2007","journal-title":"Mod Pathol"},{"issue":"4","key":"e_1_2_11_20_1","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1053\/hp.2000.6711","article-title":"The expression of ep\u2010CAM (17\u20101A) in squamous cell cancers of the lung","volume":"31","author":"Piyathilake CJ","year":"2000","journal-title":"Hum Pathol"},{"issue":"1","key":"e_1_2_11_21_1","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/sj.bjc.6602924","article-title":"Frequent high\u2010level expression of the immunotherapeutic target ep\u2010CAM in colon, stomach, prostate and lung cancers","volume":"94","author":"Went P","year":"2006","journal-title":"Br J Cancer"},{"issue":"12","key":"e_1_2_11_22_1","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.1016\/j.biocel.2013.09.008","article-title":"Epithelial cell adhesion molecule (EpCAM) is associated with prostate cancer metastasis and chemo\/radioresistance via the PI3K\/Akt\/mTOR signaling pathway","volume":"45","author":"Ni J","year":"2013","journal-title":"Int J Biochem Cell Biol"},{"issue":"1","key":"e_1_2_11_23_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41419-017-0013-8","article-title":"Epithelial cell adhesion molecule overexpression regulates epithelial\u2010mesenchymal transition, stemness and metastasis of nasopharyngeal carcinoma cells via the PTEN\/AKT\/mTOR pathway","volume":"9","author":"Wang MH","year":"2018","journal-title":"Cell Death Dis"},{"issue":"6","key":"e_1_2_11_24_1","doi-asserted-by":"crossref","first-page":"R124","DOI":"10.1186\/bcr3070","article-title":"Activator protein 1 (AP\u20101) contributes to EpCAM\u2010dependent breast cancer invasion","volume":"13","author":"Sankpal NV","year":"2011","journal-title":"Breast Cancer Res"},{"issue":"4","key":"e_1_2_11_25_1","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1158\/1541-7786.MCR-12-0518","article-title":"EpCAM modulates NF\u2010kappaB signaling and interleukin\u20108 expression in breast cancer","volume":"11","author":"Sankpal NV","year":"2013","journal-title":"Mol Cancer Res"},{"issue":"1","key":"e_1_2_11_26_1","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1186\/s12885-025-14455-8","article-title":"Landscape of cancer associated EpCAM mutations: molecular modeling, predictive insights and impact on patient survival","volume":"25","author":"Dhotare PS","year":"2025","journal-title":"BMC Cancer"},{"issue":"5","key":"e_1_2_11_27_1","first-page":"1817","article-title":"Clinicopathological implications of EpCAM expression in adenocarcinoma of the lung","volume":"29","author":"Kim Y","year":"2009","journal-title":"Anticancer Res"},{"issue":"5","key":"e_1_2_11_28_1","first-page":"1061","article-title":"CpG island methylation status in the EpCAM promoter region and gene expression","volume":"20","author":"Yu G","year":"2008","journal-title":"Oncol Rep"},{"issue":"2","key":"e_1_2_11_29_1","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1002\/ijc.23476","article-title":"Persistent downregulation of the pancarcinoma\u2010associated epithelial cell adhesion molecule via active intranuclear methylation","volume":"123","author":"Gun BTF","year":"2008","journal-title":"Int J Cancer"},{"issue":"26","key":"e_1_2_11_30_1","doi-asserted-by":"crossref","first-page":"3706","DOI":"10.1038\/onc.2016.504","article-title":"A double\u2010negative feedback loop between EpCAM and ERK contributes to the regulation of epithelial\u2010mesenchymal transition in cancer","volume":"36","author":"Sankpal NV","year":"2017","journal-title":"Oncogene"},{"key":"e_1_2_11_31_1","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2020.597673","article-title":"EpCAM\u2010mediated cellular plasticity promotes radiation resistance and metastasis in breast cancer","volume":"8","author":"Mal A","year":"2020","journal-title":"Front Cell Dev Biol"},{"issue":"6","key":"e_1_2_11_32_1","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s13402-018-0399-z","article-title":"Drug\u2010induced expression of EpCAM contributes to therapy resistance in esophageal adenocarcinoma","volume":"41","author":"Sun X","year":"2018","journal-title":"Cell Oncol (Dordr)"},{"issue":"1","key":"e_1_2_11_33_1","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1186\/s12885-021-08239-z","article-title":"Cancer\u2010associated mutations reveal a novel role for EpCAM as an inhibitor of cathepsin\u2010L and tumor cell invasion","volume":"21","author":"Sankpal NV","year":"2021","journal-title":"BMC Cancer"},{"issue":"7","key":"e_1_2_11_34_1","doi-asserted-by":"crossref","DOI":"10.3390\/biom11070956","article-title":"Functional implications of the dynamic regulation of EpCAM during epithelial\u2010to\u2010mesenchymal transition","volume":"11","author":"Brown TC","year":"2021","journal-title":"Biomolecules"},{"issue":"16","key":"e_1_2_11_35_1","doi-asserted-by":"crossref","first-page":"5818","DOI":"10.1158\/0008-5472.CAN-04-0754","article-title":"EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy","volume":"64","author":"Osta WA","year":"2004","journal-title":"Cancer Res"},{"issue":"5","key":"e_1_2_11_36_1","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1136\/jcp.2011.090274","article-title":"EpCAM expression in primary tumour tissues and metastases: an immunohistochemical analysis","volume":"64","author":"Spizzo G","year":"2011","journal-title":"J Clin Pathol"},{"issue":"1","key":"e_1_2_11_37_1","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1158\/1078-0432.CCR-12-1558","article-title":"An epithelial\u2010mesenchymal transition gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR inhibitor resistance","volume":"19","author":"Byers LA","year":"2013","journal-title":"Clin Cancer Res"},{"issue":"2","key":"e_1_2_11_38_1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/ijc.25704","article-title":"Gene expression profiling reveals novel biomarkers in nonsmall cell lung cancer","volume":"129","author":"Sanchez\u2010Palencia A","year":"2011","journal-title":"Int J Cancer"},{"issue":"2","key":"e_1_2_11_39_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0001651","article-title":"Gene expression signature of cigarette smoking and its role in lung adenocarcinoma development and survival","volume":"3","author":"Landi MT","year":"2008","journal-title":"PLoS One"},{"issue":"1","key":"e_1_2_11_40_1","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1158\/1078-0432.CCR-12-1139","article-title":"Biomarker discovery in non\u2010small cell lung cancer: integrating gene expression profiling, meta\u2010analysis, and tissue microarray validation","volume":"19","author":"Botling J","year":"2013","journal-title":"Clin Cancer Res"},{"issue":"1","key":"e_1_2_11_41_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1097\/JTO.0000000000000042","article-title":"Validation of a histology\u2010independent prognostic gene signature for early\u2010stage, non\u2010small\u2010cell lung cancer including stage IA patients","volume":"9","author":"Der SD","year":"2014","journal-title":"J Thorac Oncol"},{"issue":"7074","key":"e_1_2_11_42_1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nature04296","article-title":"Oncogenic pathway signatures in human cancers as a guide to targeted therapies","volume":"439","author":"Bild AH","year":"2006","journal-title":"Nature"},{"issue":"22","key":"e_1_2_11_43_1","doi-asserted-by":"crossref","first-page":"7397","DOI":"10.1158\/1078-0432.CCR-07-4937","article-title":"Prediction of recurrence\u2010free survival in postoperative non\u2010small cell lung cancer patients by using an integrated model of clinical information and gene expression","volume":"14","author":"Lee ES","year":"2008","journal-title":"Clin Cancer Res"},{"issue":"15","key":"e_1_2_11_44_1","doi-asserted-by":"crossref","first-page":"7466","DOI":"10.1158\/0008-5472.CAN-06-1191","article-title":"Gene expression signatures for predicting prognosis of squamous cell and adenocarcinomas of the lung","volume":"66","author":"Raponi M","year":"2006","journal-title":"Cancer Res"},{"issue":"22","key":"e_1_2_11_45_1","doi-asserted-by":"crossref","first-page":"2892","DOI":"10.1093\/bioinformatics\/btt492","article-title":"Strengths and limitations of microarray\u2010based phenotype prediction: lessons learned from the IMPROVER diagnostic signature challenge","volume":"29","author":"Tarca AL","year":"2013","journal-title":"Bioinformatics"},{"issue":"1","key":"e_1_2_11_46_1","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1158\/0008-5472.CAN-11-1403","article-title":"Identification of genes upregulated in ALK\u2010positive and EGFR\/KRAS\/ALK\u2010negative lung adenocarcinomas","volume":"72","author":"Okayama H","year":"2012","journal-title":"Cancer Res"},{"issue":"186","key":"e_1_2_11_47_1","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3005723","article-title":"Ectopic activation of germline and placental genes identifies aggressive metastasis\u2010prone lung cancers","volume":"5","author":"Rousseaux S","year":"2013","journal-title":"Sci Transl Med"},{"key":"e_1_2_11_48_1","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms5764","article-title":"Crystal structure and its bearing towards an understanding of key biological functions of EpCAM","volume":"5","author":"Pavsic M","year":"2014","journal-title":"Nat Commun"},{"issue":"28","key":"e_1_2_11_49_1","doi-asserted-by":"crossref","first-page":"25017","DOI":"10.18632\/oncotarget.4496","article-title":"Detection of soluble EpCAM (sEpCAM) in malignant ascites predicts poor overall survival in patients treated with catumaxomab","volume":"6","author":"Seeber A","year":"2015","journal-title":"Oncotarget"},{"issue":"1","key":"e_1_2_11_50_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.4161\/mabs.3.1.14193","article-title":"Concentrations of EpCAM ectodomain as found in sera of cancer patients do not significantly impact redirected lysis and T\u2010cell activation by EpCAM\/CD3\u2010bispecific BiTE antibody MT110","volume":"3","author":"Petsch S","year":"2011","journal-title":"MAbs"},{"issue":"5","key":"e_1_2_11_51_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41419-019-1601-6","article-title":"AXL degradation in combination with EGFR\u2010TKI can delay and overcome acquired resistance in human non\u2010small cell lung cancer cells","volume":"10","author":"Kim D","year":"2019","journal-title":"Cell Death Dis"},{"key":"e_1_2_11_52_1","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms6712","article-title":"Low MITF\/AXL ratio predicts early resistance to multiple targeted drugs in melanoma","volume":"5","author":"Muller J","year":"2014","journal-title":"Nat Commun"},{"issue":"6","key":"e_1_2_11_53_1","doi-asserted-by":"crossref","first-page":"3352","DOI":"10.1073\/pnas.061615598","article-title":"Heparin and cancer revisited: mechanistic connections involving platelets, P\u2010selectin, carcinoma mucins, and tumor metastasis","volume":"98","author":"Borsig L","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"issue":"6","key":"e_1_2_11_54_1","first-page":"1295","article-title":"Lysis of tumor cells by natural killer cells in mice is impeded by platelets","volume":"59","author":"Nieswandt B","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_11_55_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.lungcan.2022.02.008","article-title":"EpCAM\u2010positive disseminated cancer cells in bone marrow impact on survival of early\u2010stage NSCLC patients","volume":"167","author":"Mederer T","year":"2022","journal-title":"Lung Cancer"},{"issue":"1","key":"e_1_2_11_56_1","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.humpath.2003.08.026","article-title":"Frequent EpCam protein expression in human carcinomas","volume":"35","author":"Went PT","year":"2004","journal-title":"Hum Pathol"},{"key":"e_1_2_11_57_1","doi-asserted-by":"crossref","DOI":"10.1186\/s12885-015-1371-1","article-title":"Soluble EpCAM levels in ascites correlate with positive cytology and neutralize catumaxomab activity in vitro","volume":"15","author":"Seeber A","year":"2015","journal-title":"BMC Cancer"},{"issue":"1","key":"e_1_2_11_58_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/s41392-024-02121-7","article-title":"AXL signaling in cancer: from molecular insights to targeted therapies","volume":"10","author":"Yadav M","year":"2025","journal-title":"Signal Transduct Target Ther"},{"issue":"3","key":"e_1_2_11_59_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.xcrm.2022.100554","article-title":"AXL targeting restores PD\u20101 blockade sensitivity of STK11\/LKB1 mutant NSCLC through expansion of TCF1(+) CD8 T\u00a0cells","volume":"3","author":"Li H","year":"2022","journal-title":"Cell Rep Med"},{"key":"e_1_2_11_60_1","article-title":"The role of proteasome inhibition in nonsmall cell lung cancer","volume":"2011","author":"Escobar M","year":"2011","journal-title":"J Biomed Biotechnol"},{"issue":"57","key":"e_1_2_11_61_1","doi-asserted-by":"crossref","first-page":"97061","DOI":"10.18632\/oncotarget.21221","article-title":"Proteasome inhibitor bortezomib enhances the effect of standard chemotherapy in small cell lung cancer","volume":"8","author":"Taromi S","year":"2017","journal-title":"Oncotarget"},{"issue":"15","key":"e_1_2_11_62_1","doi-asserted-by":"crossref","first-page":"s4647","DOI":"10.1158\/1078-0432.CCR-07-0334","article-title":"Incorporating bortezomib into the treatment of lung cancer","volume":"13","author":"Davies AM","year":"2007","journal-title":"Clin Cancer Res"},{"issue":"9","key":"e_1_2_11_63_1","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1038\/sj.bjc.6605043","article-title":"Phase I study of bortezomib and cetuximab in patients with solid tumours expressing epidermal growth factor receptor","volume":"100","author":"Dudek AZ","year":"2009","journal-title":"Br J Cancer"},{"issue":"1","key":"e_1_2_11_64_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1182\/blood-2006-10-054502","article-title":"Proteasome inhibitor bortezomib impairs both myelofibrosis and osteosclerosis induced by high thrombopoietin levels in mice","volume":"110","author":"Wagner\u2010Ballon O","year":"2007","journal-title":"Blood"},{"issue":"29","key":"e_1_2_11_65_1","doi-asserted-by":"crossref","first-page":"13069","DOI":"10.1073\/pnas.1002985107","article-title":"Efficacy of bortezomib in a direct xenograft model of primary effusion lymphoma","volume":"107","author":"Sarosiek KA","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1","key":"e_1_2_11_66_1","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1631\/jzus.B1900551","article-title":"Carfilzomib inhibits the growth of lung adenocarcinoma via upregulation of Gadd45a expression","volume":"21","author":"Yang F","year":"2020","journal-title":"J Zhejiang Univ Sci B"},{"issue":"12","key":"e_1_2_11_67_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0144825","article-title":"KRAS genotype correlates with proteasome inhibitor Ixazomib activity in preclinical in vivo models of colon and non\u2010small cell lung cancer: potential role of tumor metabolism","volume":"10","author":"Chattopadhyay N","year":"2015","journal-title":"PLoS One"},{"issue":"11","key":"e_1_2_11_68_1","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.3324\/haematol.2013.089334","article-title":"Integrated safety profile of single\u2010agent carfilzomib: experience from 526 patients enrolled in 4 phase II clinical studies","volume":"98","author":"Siegel D","year":"2013","journal-title":"Haematologica"},{"issue":"17","key":"e_1_2_11_69_1","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1056\/NEJMoa1516282","article-title":"Oral Ixazomib, lenalidomide, and dexamethasone for multiple myeloma","volume":"374","author":"Moreau P","year":"2016","journal-title":"N Engl J Med"},{"issue":"2","key":"e_1_2_11_70_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s40268-019-0269-9","article-title":"Bortezomib for the treatment of hematologic malignancies: 15\u2009years later","volume":"19","author":"Robak P","year":"2019","journal-title":"Drugs R D"},{"issue":"13","key":"e_1_2_11_71_1","doi-asserted-by":"crossref","first-page":"5368","DOI":"10.1158\/0008-5472.CAN-09-3763","article-title":"ADAM17 regulates epidermal growth factor receptor expression through the activation of Notch1 in non\u2010small cell lung cancer","volume":"70","author":"Baumgart A","year":"2010","journal-title":"Cancer Res"}],"container-title":["Molecular Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1878-0261.70342","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/1878-0261.70342","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1878-0261.70342","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:05:02Z","timestamp":1791270302000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1002\/1878-0261.70342"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,6]]},"references-count":70,"alternative-id":["10.1002\/1878-0261.70342"],"URL":"https:\/\/doi.org\/10.1002\/1878-0261.70342","archive":["Portico"],"relation":{},"ISSN":["1574-7891","1878-0261"],"issn-type":[{"value":"1574-7891","type":"print"},{"value":"1878-0261","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,6]]},"assertion":[{"value":"2025-12-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1878-0261.70342"}}