{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:13:26Z","timestamp":1791922406394,"version":"4.3.4"},"reference-count":101,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Transl Oncol"],"DOI":"10.1007\/s12094-026-04331-7","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T19:21:05Z","timestamp":1774984865000},"page":"3615-3631","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Exploring tyrosine kinase inhibitors for HER2-positive breast cancer: comprehensive review on a complete pharmacology-molecular mechanisms, safety profiles, and insights from preclinical and clinical studies"],"prefix":"10.1007","volume":"28","author":[{"given":"Meghraj V.","family":"Suryawanshi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rukaiya T.","family":"Girase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal S.","family":"Bagul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8086-7821","authenticated-orcid":false,"given":"Pranjal P.","family":"Gujarathi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"4331_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2024.155607","volume":"263","author":"V Sankarapandian","year":"2024","unstructured":"Sankarapandian V, Rajendran RL, Miruka CO, Sivamani P, Maran BAV, Krishnamoorthy R, et al. A review on tyrosine kinase inhibitors for targeted breast cancer therapy. Pathol Res Pract. 2024;263:155607. https:\/\/doi.org\/10.1016\/j.prp.2024.155607.","journal-title":"Pathol Res Pract"},{"key":"4331_CR2","doi-asserted-by":"publisher","first-page":"e380","DOI":"10.1016\/j.clbc.2023.05.003","volume":"23","author":"SL Graff","year":"2023","unstructured":"Graff SL, Yan F, Abdou Y. Newly approved and emerging agents in HER2-positive metastatic breast cancer. Clin Breast Cancer. 2023;23:e380\u201393. https:\/\/doi.org\/10.1016\/j.clbc.2023.05.003.","journal-title":"Clin Breast Cancer"},{"key":"4331_CR3","unstructured":"https:\/\/www.iarc.who.int\/cancer-type\/breast-cancer\/ [Internet]. [cited 2026 Feb 22]. https:\/\/www.iarc.who.int\/cancer-type\/breast-cancer\/. Accessed 22 Feb 2026"},{"key":"4331_CR4","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1089066","author":"DD Singh","year":"2022","unstructured":"Singh DD, Lee H-J, Yadav DK. Clinical updates on tyrosine kinase inhibitors in HER2-positive breast cancer. Front Pharmacol. 2022. https:\/\/doi.org\/10.3389\/fphar.2022.1089066.","journal-title":"Front Pharmacol"},{"key":"4331_CR5","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15071987","volume":"15","author":"MF Mercogliano","year":"2023","unstructured":"Mercogliano MF, Bruni S, Mauro FL, Schillaci R. Emerging targeted therapies for HER2-positive breast cancer. Cancers (Basel). 2023;15:1987. https:\/\/doi.org\/10.3390\/cancers15071987.","journal-title":"Cancers (Basel)"},{"key":"4331_CR6","doi-asserted-by":"publisher","first-page":"2787","DOI":"10.1200\/JCO.2003.01.504","volume":"21","author":"J Mendelsohn","year":"2003","unstructured":"Mendelsohn J, Baselga J. Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol. 2003;21:2787\u201399. https:\/\/doi.org\/10.1200\/JCO.2003.01.504.","journal-title":"J Clin Oncol"},{"key":"4331_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.breast.2012.09.008","volume":"22","author":"DL Nielsen","year":"2013","unstructured":"Nielsen DL, K\u00fcmler I, Palshof JAE, Andersson M. Efficacy of HER2-targeted therapy in metastatic breast cancer. Monoclonal antibodies and tyrosine kinase inhibitors. Breast. 2013;22:1\u201312. https:\/\/doi.org\/10.1016\/j.breast.2012.09.008.","journal-title":"Breast"},{"key":"4331_CR8","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.ccr.2014.02.025","volume":"25","author":"CL Arteaga","year":"2014","unstructured":"Arteaga CL, Engelman JA. ERBB receptors: From oncogene discovery to basic science to mechanism-based cancer therapeutics. Cancer Cell. 2014;25:282\u2013303. https:\/\/doi.org\/10.1016\/j.ccr.2014.02.025.","journal-title":"Cancer Cell"},{"key":"4331_CR9","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-024-00565-1","volume":"12","author":"K Zhu","year":"2024","unstructured":"Zhu K, Yang X, Tai H, Zhong X, Luo T, Zheng H. HER2-targeted therapies in cancer: a systematic review. Biomark Res. 2024;12:16. https:\/\/doi.org\/10.1186\/s40364-024-00565-1.","journal-title":"Biomark Res"},{"key":"4331_CR10","doi-asserted-by":"publisher","DOI":"10.1136\/esmoopen-2017-000279","volume":"2","author":"CM Connell","year":"2017","unstructured":"Connell CM, Doherty GJ. Activating HER2 mutations as emerging targets in multiple solid cancers. ESMO Open. 2017;2:e000279. https:\/\/doi.org\/10.1136\/esmoopen-2017-000279.","journal-title":"ESMO Open"},{"key":"4331_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2012\/743193","volume":"2012","author":"Z Mitri","year":"2012","unstructured":"Mitri Z, Constantine T, O\u2019Regan R. The HER2 receptor in breast cancer: Pathophysiology, clinical use, and new advances in therapy. Chemother Res Pract. 2012;2012:1\u20137. https:\/\/doi.org\/10.1155\/2012\/743193.","journal-title":"Chemother Res Pract"},{"key":"4331_CR12","doi-asserted-by":"publisher","first-page":"115","DOI":"10.2147\/OTT.S335934","volume":"16","author":"P Mand\u00f3","year":"2023","unstructured":"Mand\u00f3 P, Waisberg F, Pasquinelli R, Rivero S, Ostinelli A, Perazzo F. HER2-directed therapy in advanced breast cancer: Benefits and risks. Onco Targets Ther. 2023;16:115\u201332. https:\/\/doi.org\/10.2147\/OTT.S335934.","journal-title":"Onco Targets Ther"},{"key":"4331_CR13","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.2286","volume":"1","author":"MM Moasser","year":"2015","unstructured":"Moasser MM, Krop IE. The evolving landscape of HER2 targeting in breast cancer. JAMA Oncol. 2015;1:1154. https:\/\/doi.org\/10.1001\/jamaoncol.2015.2286.","journal-title":"JAMA Oncol"},{"key":"4331_CR14","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/S0014-4827(02)00040-X","volume":"284","author":"U Vijapurkar","year":"2003","unstructured":"Vijapurkar U, Kim M-S, Koland JG. Roles of mitogen-activated protein kinase and phosphoinositide 3\u2032-kinase in ErbB2\/ErbB3 coreceptor-mediated heregulin signaling\u2606. Exp Cell Res. 2003;284:289\u2013300. https:\/\/doi.org\/10.1016\/S0014-4827(02)00040-X.","journal-title":"Exp Cell Res"},{"key":"4331_CR15","volume":"19","author":"FJ Esteva","year":"2005","unstructured":"Esteva FJ, Pusztai L. Optimizing outcomes in HER2-positive breast cancer: the molecular rationale. Oncology (Williston Park). 2005;19:4.","journal-title":"Oncology (Williston Park)"},{"key":"4331_CR16","doi-asserted-by":"publisher","first-page":"viii15","DOI":"10.1093\/annonc\/mdl983","volume":"17","author":"P Kanavos","year":"2006","unstructured":"Kanavos P. The rising burden of cancer in the developing world. Ann Oncol. 2006;17:viii15-23. https:\/\/doi.org\/10.1093\/annonc\/mdl983.","journal-title":"Ann Oncol"},{"key":"4331_CR17","doi-asserted-by":"publisher","DOI":"10.1186\/1756-8722-6-38","volume":"6","author":"JA Incorvati","year":"2013","unstructured":"Incorvati JA, Shah S, Mu Y, Lu J. Targeted therapy for HER2 positive breast cancer. J Hematol Oncol. 2013;6:38. https:\/\/doi.org\/10.1186\/1756-8722-6-38.","journal-title":"J Hematol Oncol"},{"key":"4331_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/s41523-021-00265-1","volume":"7","author":"I Schlam","year":"2021","unstructured":"Schlam I, Swain SM. HER2-positive breast cancer and tyrosine kinase inhibitors: the time is now. npj Breast Cancer. 2021;7:56. https:\/\/doi.org\/10.1038\/s41523-021-00265-1.","journal-title":"npj Breast Cancer"},{"key":"4331_CR19","doi-asserted-by":"publisher","first-page":"3138","DOI":"10.1200\/JCO.20.00147","volume":"38","author":"C Saura","year":"2020","unstructured":"Saura C, Oliveira M, Feng Y-H, Dai M-S, Chen S-W, Hurvitz SA, et al. Neratinib plus capecitabine versus lapatinib plus capecitabine in HER2-positive metastatic breast cancer previously treated with \u2265 2 HER2-directed regimens: Phase III NALA trial. J Clin Oncol. 2020;38:3138\u201349. https:\/\/doi.org\/10.1200\/JCO.20.00147.","journal-title":"J Clin Oncol"},{"key":"4331_CR20","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.0237","volume":"2","author":"A Awada","year":"2016","unstructured":"Awada A, Colomer R, Inoue K, Bondarenko I, Badwe RA, Demetriou G, et al. Neratinib plus paclitaxel vs trastuzumab plus paclitaxel in previously untreated metastatic ERBB2-positive breast cancer. JAMA Oncol. 2016;2:1557. https:\/\/doi.org\/10.1001\/jamaoncol.2016.0237.","journal-title":"JAMA Oncol"},{"key":"4331_CR21","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.576926","author":"M Khan","year":"2020","unstructured":"Khan M, Zhao Z, Arooj S, Zheng T, Liao G. Lapatinib plus local radiation therapy for brain metastases from HER-2 positive breast cancer patients and role of trastuzumab: a systematic review and meta-analysis. Front Oncol. 2020. https:\/\/doi.org\/10.3389\/fonc.2020.576926.","journal-title":"Front Oncol."},{"key":"4331_CR22","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1492203","author":"X Zhang","year":"2025","unstructured":"Zhang X, Yin Y, Yu Q, Chen X, Cheng Y. Review of the clinical status of cardiotoxicity of HER-2 positive breast cancer targeted therapeutic drugs. Front Oncol. 2025. https:\/\/doi.org\/10.3389\/fonc.2024.1492203.","journal-title":"Front Oncol."},{"key":"4331_CR23","doi-asserted-by":"publisher","first-page":"15090","DOI":"10.1002\/cam4.6180","volume":"12","author":"Y Yu","year":"2023","unstructured":"Yu Y, Huang K, Lin Y, Zhang J, Song C. Tyrosine kinase inhibitors in <scp>HER2<\/scp> \u2010positive breast cancer brain metastases: a systematic review and meta\u2010analysis. Cancer Med. 2023;12:15090\u2013100. https:\/\/doi.org\/10.1002\/cam4.6180.","journal-title":"Cancer Med"},{"key":"4331_CR24","first-page":"2103","volume":"9","author":"J-C Xuhong","year":"2019","unstructured":"Xuhong J-C, Qi X-W, Zhang Y, Jiang J. Mechanism, safety and efficacy of three tyrosine kinase inhibitors lapatinib, neratinib and pyrotinib in HER2-positive breast cancer. Am J Cancer Res. 2019;9:2103\u201319.","journal-title":"Am J Cancer Res"},{"key":"4331_CR25","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13051153","volume":"13","author":"H Miski","year":"2025","unstructured":"Miski H, Krupa K, Budzik MP, Depta\u0142a A, Badowska-Kozakiewicz A. HER2-positive breast cancer\u2014current treatment management and new therapeutic methods for brain metastasis. Biomedicines. 2025;13:1153. https:\/\/doi.org\/10.3390\/biomedicines13051153.","journal-title":"Biomedicines"},{"key":"4331_CR26","doi-asserted-by":"publisher","DOI":"10.1186\/s13058-025-02013-w","volume":"27","author":"J Han","year":"2025","unstructured":"Han J, Zhai X, Tao X, Li Y, Zhao Z, Yu Z, et al. Pharmacovigilance study of adverse reactions of anti-HER-2 drugs for the treatment of HER-2-positive breast cancer based on the FAERS database. Breast Cancer Res. 2025;27:54. https:\/\/doi.org\/10.1186\/s13058-025-02013-w.","journal-title":"Breast Cancer Res"},{"key":"4331_CR27","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-023-00736-0","volume":"29","author":"L Guo","year":"2023","unstructured":"Guo L, Shao W, Zhou C, Yang H, Yang L, Cai Q, et al. Neratinib for HER2-positive breast cancer with an overlooked option. Mol Med. 2023;29:134. https:\/\/doi.org\/10.1186\/s10020-023-00736-0.","journal-title":"Mol Med"},{"key":"4331_CR28","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1007\/s10549-021-06313-5","volume":"189","author":"MS Dai","year":"2021","unstructured":"Dai MS, Feng YH, Chen SW, Masuda N, Yau T, Chen ST, et al. Analysis of the pan-Asian subgroup of patients in the NALA Trial: a randomized phase III NALA Trial comparing neratinib+capecitabine (N+C) vs lapatinib+capecitabine (L+C) in patients with HER2+metastatic breast cancer (mBC) previously treated with two or more HER2-directed regimens. Breast Cancer Res Treat. 2021;189:665\u201376. https:\/\/doi.org\/10.1007\/s10549-021-06313-5.","journal-title":"Breast Cancer Res Treat"},{"key":"4331_CR29","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-020-07143-2","volume":"20","author":"C Wang","year":"2020","unstructured":"Wang C, Lin Y, Zhou Y, Mao F, Zhu H, Guan J, et al. Pyrotinib with trastuzumab and aromatase inhibitors as first-line treatment for HER2 positive and hormone receptor positive metastatic or locally advanced breast cancer: study protocol of a randomized controlled trial. BMC Cancer. 2020;20:653. https:\/\/doi.org\/10.1186\/s12885-020-07143-2.","journal-title":"BMC Cancer"},{"key":"4331_CR30","doi-asserted-by":"publisher","DOI":"10.1007\/s12672-025-02820-9","volume":"16","author":"J Luo","year":"2025","unstructured":"Luo J, Ren A, Si D, Yang J, Xu D, Li N. Drug treatment of breast cancer brain metastases: progress and challenges. Discov Oncol. 2025;16:1025. https:\/\/doi.org\/10.1007\/s12672-025-02820-9.","journal-title":"Discov Oncol"},{"key":"4331_CR31","doi-asserted-by":"publisher","DOI":"10.1177\/1533033820962140","author":"X Yang","year":"2020","unstructured":"Yang X, Wu D, Yuan S. Tyrosine kinase inhibitors in the combination therapy of HER2 positive breast cancer. Technol Cancer Res Treat. 2020. https:\/\/doi.org\/10.1177\/1533033820962140.","journal-title":"Technol Cancer Res Treat"},{"key":"4331_CR32","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/B978-0-443-18616-5.00011-9","volume-title":"Fused Pyrimidine-Based Drug Discovery","author":"S Arora","year":"2023","unstructured":"Arora S, Kumar R. FDA approved six-membered ring fused pyrimidine-based derivatives. In: Fused Pyrimidine-Based Drug Discovery. Elsevier; 2023. p. 221\u201348."},{"key":"4331_CR33","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1447508","author":"C von Arx","year":"2024","unstructured":"von Arx C, Calderaio C, Calabrese A, Marciano B, Martinelli C, Di Lauro V, et al. The multidisciplinary management of HER2-positive breast cancer brain metastases: from new biological insights to future therapeutic options. Front Oncol. 2024. https:\/\/doi.org\/10.3389\/fonc.2024.1447508.","journal-title":"Front Oncol"},{"key":"4331_CR34","doi-asserted-by":"publisher","first-page":"2610","DOI":"10.1200\/JCO.20.00775","volume":"38","author":"NU Lin","year":"2020","unstructured":"Lin NU, Borges V, Anders C, Murthy RK, Paplomata E, Hamilton E, et al. Intracranial efficacy and survival with tucatinib plus trastuzumab and capecitabine for previously treated HER2-positive breast cancer with brain metastases in the HER2CLIMB Trial. J Clin Oncol. 2020;38:2610\u20139. https:\/\/doi.org\/10.1200\/JCO.20.00775.","journal-title":"J Clin Oncol"},{"key":"4331_CR35","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/s40262-016-0440-1","volume":"56","author":"S Wind","year":"2017","unstructured":"Wind S, Schnell D, Ebner T, Freiwald M, Stopfer P. Clinical pharmacokinetics and pharmacodynamics of afatinib. Clin Pharmacokinet. 2017;56:235\u201350. https:\/\/doi.org\/10.1007\/s40262-016-0440-1.","journal-title":"Clin Pharmacokinet"},{"key":"4331_CR36","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26216677","volume":"26","author":"MAS Abourehab","year":"2021","unstructured":"Abourehab MAS, Alqahtani AM, Youssif BGM, Gouda AM. Globally approved EGFR inhibitors: insights into their syntheses, target kinases, biological activities, receptor interactions, and metabolism. Molecules. 2021;26:6677. https:\/\/doi.org\/10.3390\/molecules26216677.","journal-title":"Molecules"},{"key":"4331_CR37","doi-asserted-by":"publisher","DOI":"10.3390\/biom15101443","volume":"15","author":"R Ekyalongo","year":"2025","unstructured":"Ekyalongo R, Yamaoka T, Tsurutani J. Recent advances in the development and clinical use of HER2 inhibitors in non-small cell lung cancer. Biomolecules. 2025;15:1443. https:\/\/doi.org\/10.3390\/biom15101443.","journal-title":"Biomolecules"},{"key":"4331_CR38","doi-asserted-by":"publisher","first-page":"15196","DOI":"10.3390\/molecules190915196","volume":"19","author":"R Schroeder","year":"2014","unstructured":"Schroeder R, Stevens C, Sridhar J. Small molecule tyrosine kinase inhibitors of ErbB2\/HER2\/Neu in the treatment of aggressive breast cancer. Molecules. 2014;19:15196\u2013212. https:\/\/doi.org\/10.3390\/molecules190915196.","journal-title":"Molecules"},{"key":"4331_CR39","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1093\/jnci\/djn216","volume":"100","author":"B Gril","year":"2008","unstructured":"Gril B, Palmieri D, Bronder JL, Herring JM, Vega-Valle E, Feigenbaum L, et al. Effect of lapatinib on the outgrowth of metastatic breast cancer cells to the brain. J Natl Cancer Inst. 2008;100:1092\u2013103. https:\/\/doi.org\/10.1093\/jnci\/djn216.","journal-title":"J Natl Cancer Inst"},{"key":"4331_CR40","doi-asserted-by":"publisher","first-page":"1846","DOI":"10.1158\/1535-7163.MCT-08-0168","volume":"7","author":"D Zhang","year":"2008","unstructured":"Zhang D, Pal A, Bornmann WG, Yamasaki F, Esteva FJ, Hortobagyi GN, et al. Activity of lapatinib is independent of EGFR expression level in HER2-overexpressing breast cancer cells. Mol Cancer Ther. 2008;7:1846\u201350. https:\/\/doi.org\/10.1158\/1535-7163.MCT-08-0168.","journal-title":"Mol Cancer Ther"},{"key":"4331_CR41","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1158\/1078-0432.CCR-09-1112","volume":"16","author":"ZA Wainberg","year":"2010","unstructured":"Wainberg ZA, Anghel A, Desai AJ, Ayala R, Luo T, Safran B, et al. Lapatinib, a dual EGFR and HER2 kinase inhibitor, selectively inhibits HER2-amplified human gastric cancer cells and is synergistic with trastuzumab in vitro and in vivo. Clin Cancer Res. 2010;16:1509\u201319. https:\/\/doi.org\/10.1158\/1078-0432.CCR-09-1112.","journal-title":"Clin Cancer Res"},{"key":"4331_CR42","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1158\/0008-5472.CAN-10-3795","volume":"71","author":"J Arribas","year":"2011","unstructured":"Arribas J, Baselga J, Pedersen K, Parra-Palau JL. p95HER2 and breast cancer. Cancer Res. 2011;71:1515\u20139. https:\/\/doi.org\/10.1158\/0008-5472.CAN-10-3795.","journal-title":"Cancer Res"},{"key":"4331_CR43","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1158\/1078-0432.CCR-05-1807","volume":"12","author":"R S\u00e1ez","year":"2006","unstructured":"S\u00e1ez R, Molina MA, Ramsey EE, Rojo F, Keenan EJ, Albanell J, et al. p95HER-2 predicts worse outcome in patients with HER-2-positive breast cancer. Clin Cancer Res. 2006;12:424\u201331. https:\/\/doi.org\/10.1158\/1078-0432.CCR-05-1807.","journal-title":"Clin Cancer Res"},{"key":"4331_CR44","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1093\/jnci\/djk134","volume":"99","author":"M Scaltriti","year":"2007","unstructured":"Scaltriti M, Rojo F, Ocana A, Anido J, Guzman M, Cortes J, et al. Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer. J Natl Cancer Inst. 2007;99:628\u201338. https:\/\/doi.org\/10.1093\/jnci\/djk134.","journal-title":"J Natl Cancer Inst"},{"key":"4331_CR45","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1200\/JCO.2013.52.1161","volume":"32","author":"AJ Chien","year":"2014","unstructured":"Chien AJ, Munster PN, Melisko ME, Rugo HS, Park JW, Goga A, et al. Phase I dose-escalation study of 5-day intermittent oral lapatinib therapy in patients with human epidermal growth factor receptor 2\u2013overexpressing breast cancer. J Clin Oncol. 2014;32:1472\u20139. https:\/\/doi.org\/10.1200\/JCO.2013.52.1161.","journal-title":"J Clin Oncol"},{"key":"4331_CR46","doi-asserted-by":"publisher","first-page":"3958","DOI":"10.1158\/0008-5472.CAN-03-2868","volume":"64","author":"SK Rabindran","year":"2004","unstructured":"Rabindran SK, Discafani CM, Rosfjord EC, Baxter M, Floyd MB, Golas J, et al. Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase. Cancer Res. 2004;64:3958\u201365. https:\/\/doi.org\/10.1158\/0008-5472.CAN-03-2868.","journal-title":"Cancer Res"},{"key":"4331_CR47","doi-asserted-by":"publisher","DOI":"10.1177\/15330338211037812","author":"X Wang","year":"2021","unstructured":"Wang X, Wang L, Yu Q, Liu Z, Li C, Wang F, et al. The effectiveness of Lapatinib in HER2-positive metastatic breast cancer patients pretreated with multiline Anti-HER2 treatment: A retrospective study in China. Technol Cancer Res Treat. 2021. https:\/\/doi.org\/10.1177\/15330338211037812.","journal-title":"Technol Cancer Res Treat"},{"key":"4331_CR48","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1021\/jm020241c","volume":"46","author":"A Wissner","year":"2003","unstructured":"Wissner A, Overbeek E, Reich MF, Floyd MB, Johnson BD, Mamuya N, et al. Synthesis and structure\u2212activity relationships of 6,7-disubstituted 4-anilinoquinoline-3-carbonitriles. The design of an orally active, irreversible inhibitor of the tyrosine kinase activity of the Epidermal Growth Factor Receptor (EGFR) and the Human Epidermal Growth Factor Receptor-2 (HER-2). J Med Chem. 2003;46:49\u201363. https:\/\/doi.org\/10.1021\/jm020241c.","journal-title":"J Med Chem"},{"key":"4331_CR49","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1002\/ardp.200800009","volume":"341","author":"A Wissner","year":"2008","unstructured":"Wissner A, Mansour TS. The development of HKI\u2010272 and related compounds for the treatment of cancer. Arch Pharm (Weinheim). 2008;341:465\u201377. https:\/\/doi.org\/10.1002\/ardp.200800009.","journal-title":"Arch Pharm (Weinheim)"},{"key":"4331_CR50","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1021\/jm040159c","volume":"48","author":"H-R Tsou","year":"2005","unstructured":"Tsou H-R, Overbeek-Klumpers EG, Hallett WA, Reich MF, Floyd MB, Johnson BD, et al. Optimization of 6,7-Disubstituted-4-(arylamino)quinoline-3-carbonitriles as orally active, irreversible inhibitors of human epidermal growth factor receptor-2 kinase activity. J Med Chem. 2005;48:1107\u201331. https:\/\/doi.org\/10.1021\/jm040159c.","journal-title":"J Med Chem"},{"key":"4331_CR51","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.clbc.2018.12.011","volume":"19","author":"KL Blackwell","year":"2019","unstructured":"Blackwell KL, Zaman K, Qin S, Tkaczuk KHR, Campone M, Hunt D, et al. Neratinib in combination with Trastuzumab for the treatment of patients with advanced HER2-positive breast cancer: a phase I\/II study. Clin Breast Cancer. 2019;19:97-104.e4. https:\/\/doi.org\/10.1016\/j.clbc.2018.12.011.","journal-title":"Clin Breast Cancer"},{"key":"4331_CR52","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.canlet.2016.08.026","volume":"382","author":"Y Zhang","year":"2016","unstructured":"Zhang Y, Zhang J, Liu C, Du S, Feng L, Luan X, et al. Neratinib induces ErbB2 ubiquitylation and endocytic degradation via HSP90 dissociation in breast cancer cells. Cancer Lett. 2016;382:176\u201385. https:\/\/doi.org\/10.1016\/j.canlet.2016.08.026.","journal-title":"Cancer Lett"},{"key":"4331_CR53","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1093\/jjco\/hys012","volume":"42","author":"Y Ito","year":"2012","unstructured":"Ito Y, Suenaga M, Hatake K, Takahashi S, Yokoyama M, Onozawa Y, et al. Safety, efficacy and pharmacokinetics of Neratinib (HKI-272) in Japanese patients with advanced solid tumors: a phase 1 dose-escalation study. Jpn J Clin Oncol. 2012;42:278\u201386. https:\/\/doi.org\/10.1093\/jjco\/hys012.","journal-title":"Jpn J Clin Oncol"},{"key":"4331_CR54","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1200\/JCO.2009.25.8707","volume":"28","author":"HJ Burstein","year":"2010","unstructured":"Burstein HJ, Sun Y, Dirix LY, Jiang Z, Paridaens R, Tan AR, et al. Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer. J Clin Oncol. 2010;28:1301\u20137. https:\/\/doi.org\/10.1200\/JCO.2009.25.8707.","journal-title":"J Clin Oncol"},{"key":"4331_CR55","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.18632\/oncotarget.1148","volume":"4","author":"A Canonici","year":"2013","unstructured":"Canonici A, Gijsen M, Mullooly M, Bennett R, Bouguern N, Pedersen K, et al. Neratinib overcomes Trastuzumab resistance in HER2 amplified breast cancer. Oncotarget. 2013;4:1592\u2013605. https:\/\/doi.org\/10.18632\/oncotarget.1148.","journal-title":"Oncotarget"},{"key":"4331_CR56","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1124\/mol.111.076299","volume":"82","author":"X Zhao","year":"2012","unstructured":"Zhao X, Xie J, Chen X, Sim HM, Zhang X, Liang Y, et al. Neratinib reverses ATP-binding cassette B1-mediated chemotherapeutic drug resistance in vitro, in vivo, and ex vivo. Mol Pharmacol. 2012;82:47\u201358. https:\/\/doi.org\/10.1124\/mol.111.076299.","journal-title":"Mol Pharmacol"},{"key":"4331_CR57","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/S1470-2045(15)00551-3","volume":"17","author":"A Chan","year":"2016","unstructured":"Chan A, Delaloge S, Holmes FA, Moy B, Iwata H, Harvey VJ, et al. Neratinib after Trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016;17:367\u201377. https:\/\/doi.org\/10.1016\/S1470-2045(15)00551-3.","journal-title":"Lancet Oncol"},{"key":"4331_CR58","doi-asserted-by":"publisher","first-page":"2610","DOI":"10.1200\/JCO.19.00108","volume":"37","author":"F Ma","year":"2019","unstructured":"Ma F, Ouyang Q, Li W, Jiang Z, Tong Z, Liu Y, et al. Pyrotinib or Lapatinib combined with Capecitabine in HER2\u2013positive metastatic breast cancer with prior Taxanes, Anthracyclines, and\/or Trastuzumab: a randomized, phase II study. J Clin Oncol. 2019;37:2610\u20139. https:\/\/doi.org\/10.1200\/JCO.19.00108.","journal-title":"J Clin Oncol"},{"key":"4331_CR59","doi-asserted-by":"publisher","first-page":"3105","DOI":"10.1200\/JCO.2016.69.6179","volume":"35","author":"F Ma","year":"2017","unstructured":"Ma F, Li Q, Chen S, Zhu W, Fan Y, Wang J, et al. Phase I study and biomarker analysis of Pyrotinib, a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor, in patients with human epidermal growth factor receptor 2\u2013positive metastatic breast cancer. J Clin Oncol. 2017;35:3105\u201312. https:\/\/doi.org\/10.1200\/JCO.2016.69.6179.","journal-title":"J Clin Oncol"},{"key":"4331_CR60","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.canlet.2019.01.005","volume":"447","author":"K Zhang","year":"2019","unstructured":"Zhang K, Hong R, Kaping L, Xu F, Xia W, Qin G, et al. CDK4\/6 inhibitor palbociclib enhances the effect of pyrotinib in HER2-positive breast cancer. Cancer Lett. 2019;447:130\u201340. https:\/\/doi.org\/10.1016\/j.canlet.2019.01.005.","journal-title":"Cancer Lett"},{"key":"4331_CR61","doi-asserted-by":"publisher","first-page":"306","DOI":"10.2174\/1568009617666170623122213","volume":"18","author":"H Singla","year":"2018","unstructured":"Singla H, Munshi A, Banipal RPS, Kumar V. recent updates on the therapeutic potential of HER2 tyrosine kinase inhibitors for the treatment of breast cancer. Curr Cancer Drug Targets. 2018;18:306\u201327. https:\/\/doi.org\/10.2174\/1568009617666170623122213.","journal-title":"Curr Cancer Drug Targets"},{"key":"4331_CR62","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1038\/s41401-018-0176-6","volume":"40","author":"J Meng","year":"2019","unstructured":"Meng J, Liu X, Ma S, Zhang H, Yu S, Zhang Y, et al. Metabolism and disposition of pyrotinib in healthy male volunteers: covalent binding with human plasma protein. Acta Pharmacol Sin. 2019;40:980\u20138. https:\/\/doi.org\/10.1038\/s41401-018-0176-6.","journal-title":"Acta Pharmacol Sin"},{"key":"4331_CR63","first-page":"2531","volume":"5","author":"M Segovia-Mendoza","year":"2015","unstructured":"Segovia-Mendoza M, Gonz\u00e1lez-Gonz\u00e1lez ME, Barrera D, D\u00edaz L, Garc\u00eda-Becerra R. Efficacy and mechanism of action of the tyrosine kinase inhibitors gefitinib, lapatinib and neratinib in the treatment of HER2-positive breast cancer: preclinical and clinical evidence. Am J Cancer Res. 2015;5:2531\u201361.","journal-title":"Am J Cancer Res"},{"key":"4331_CR64","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1002\/jcp.10411","volume":"198","author":"M Campiglio","year":"2004","unstructured":"Campiglio M, Locatelli A, Olgiati C, Normanno N, Somenzi G, Vigan\u00f2 L, et al. Inhibition of proliferation and induction of apoptosis in breast cancer cells by the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor ZD1839 (\u2018Iressa\u2019) is independent of EGFR expression level. J Cell Physiol. 2004;198:259\u201368. https:\/\/doi.org\/10.1002\/jcp.10411.","journal-title":"J Cell Physiol"},{"key":"4331_CR65","doi-asserted-by":"publisher","first-page":"3169","DOI":"10.1158\/1535-7163.MCT-07-0507","volume":"6","author":"J Krol","year":"2007","unstructured":"Krol J, Francis RE, Albergaria A, Sunters A, Polychronis A, Coombes RC, et al. The transcription factor FOXO3a is a crucial cellular target of gefitinib (Iressa) in breast cancer cells. Mol Cancer Ther. 2007;6:3169\u201379. https:\/\/doi.org\/10.1158\/1535-7163.MCT-07-0507.","journal-title":"Mol Cancer Ther"},{"key":"4331_CR66","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.jsbmb.2014.12.006","volume":"148","author":"M Segovia-Mendoza","year":"2015","unstructured":"Segovia-Mendoza M, D\u00edaz L, Gonz\u00e1lez-Gonz\u00e1lez ME, Mart\u00ednez-Reza I, Garc\u00eda-Quiroz J, Prado-Garcia H, et al. Calcitriol and its analogues enhance the antiproliferative activity of gefitinib in breast cancer cells. J Steroid Biochem Mol Biol. 2015;148:122\u201331. https:\/\/doi.org\/10.1016\/j.jsbmb.2014.12.006.","journal-title":"J Steroid Biochem Mol Biol"},{"key":"4331_CR67","first-page":"1274","volume":"9","author":"J Anido","year":"2003","unstructured":"Anido J, Matar P, Albanell J, Guzm\u00e1n M, Rojo F, Arribas J, et al. ZD1839, a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, induces the formation of inactive EGFR\/HER2 and EGFR\/HER3 heterodimers and prevents heregulin signaling in HER2-overexpressing breast cancer cells. Clin Cancer Res. 2003;9:1274\u201383.","journal-title":"Clin Cancer Res"},{"key":"4331_CR68","doi-asserted-by":"publisher","first-page":"10648","DOI":"10.1038\/srep10648","volume":"5","author":"C Xue","year":"2015","unstructured":"Xue C, Hong S, Li N, Feng W, Jia J, Peng J, et al. Randomized, multicenter study of gefitinib dose-escalation in advanced non-small-cell lung cancer patients achieved stable disease after one-month gefitinib treatment. Sci Rep. 2015;5:10648. https:\/\/doi.org\/10.1038\/srep10648.","journal-title":"Sci Rep"},{"key":"4331_CR69","doi-asserted-by":"publisher","first-page":"3335","DOI":"10.1200\/JCO.2012.45.0981","volume":"31","author":"N Katakami","year":"2013","unstructured":"Katakami N, Atagi S, Goto K, Hida T, Horai T, Inoue A, et al. LUX-Lung 4: a phase II trial of afatinib in patients with advanced non\u2013small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. J Clin Oncol. 2013;31:3335\u201341. https:\/\/doi.org\/10.1200\/JCO.2012.45.0981.","journal-title":"J Clin Oncol"},{"key":"4331_CR70","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/1756-8722-7-22","volume":"7","author":"J Zhang","year":"2014","unstructured":"Zhang J, Cao J, Li J, Zhang Y, Chen Z, Peng W, et al. A phase I study of AST1306, a novel irreversible EGFR and HER2 kinase inhibitor, in patients with advanced solid tumors. J Hematol Oncol. 2014;7:22. https:\/\/doi.org\/10.1186\/1756-8722-7-22.","journal-title":"J Hematol Oncol"},{"key":"4331_CR71","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1038\/sj.bjc.6605641","volume":"102","author":"AH Evans","year":"2010","unstructured":"Evans AH, Pancholi S, Farmer I, Thornhill A, Evans DB, Johnston SR, et al. EGFR\/HER2 inhibitor AEE788 increases ER-mediated transcription in HER2\/ER-positive breast cancer cells but functions synergistically with endocrine therapy. Br J Cancer. 2010;102:1235\u201343. https:\/\/doi.org\/10.1038\/sj.bjc.6605641.","journal-title":"Br J Cancer"},{"key":"4331_CR72","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1007\/s00280-009-0975-z","volume":"64","author":"O Rixe","year":"2009","unstructured":"Rixe O, Franco SX, Yardley DA, Johnston SR, Martin M, Arun BK, et al. A randomized, phase II, dose-finding study of the pan-ErbB receptor tyrosine-kinase inhibitor CI-1033 in patients with pretreated metastatic breast cancer. Cancer Chemother Pharmacol. 2009;64:1139\u201348. https:\/\/doi.org\/10.1007\/s00280-009-0975-z.","journal-title":"Cancer Chemother Pharmacol"},{"key":"4331_CR73","doi-asserted-by":"publisher","first-page":"B268","DOI":"10.1158\/1535-7163.TARG-13-B268","volume":"12","author":"A Jimeno","year":"2013","unstructured":"Jimeno A, Galloway T, Wirth L, Gilbert J, Saba N, Bauman J, et al. Abstract B268: A Phase I Study of CUDC-101, a multitarget inhibitor of HDACs, EGFR, and HER2, in combination with chemoradiation in patients with intermediate\/high risk locally advanced squamous cell carcinoma of the head and neck. Mol Cancer Ther. 2013;12:B268\u2013B268. https:\/\/doi.org\/10.1158\/1535-7163.TARG-13-B268.","journal-title":"Mol Cancer Ther"},{"key":"4331_CR74","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1038\/bjc.2011.590","volume":"106","author":"T Doi","year":"2012","unstructured":"Doi T, Takiuchi H, Ohtsu A, Fuse N, Goto M, Yoshida M, et al. Phase I first-in-human study of TAK-285, a novel investigational dual HER2\/EGFR inhibitor, in cancer patients. Br J Cancer. 2012;106:666\u201372. https:\/\/doi.org\/10.1038\/bjc.2011.590.","journal-title":"Br J Cancer"},{"key":"4331_CR75","doi-asserted-by":"publisher","first-page":"1722","DOI":"10.1002\/hed.23822","volume":"37","author":"MJ Axelrod","year":"2015","unstructured":"Axelrod MJ, Mendez RE, Khalil A, Leimgruber SS, Sharlow ER, Capaldo B, et al. Synergistic apoptosis in head and neck squamous cell carcinoma cells by co-inhibition of insulin-like growth factor-1 receptor signaling and compensatory signaling pathways. Head Neck. 2015;37:1722\u201332. https:\/\/doi.org\/10.1002\/hed.23822.","journal-title":"Head Neck"},{"key":"4331_CR76","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1002\/cncr.28561","volume":"120","author":"KL Reckamp","year":"2014","unstructured":"Reckamp KL, Giaccone G, Camidge DR, Gadgeel SM, Khuri FR, Engelman JA, et al. A phase 2 trial of dacomitinib (PF-00299804), an oral, irreversible pan-HER (human epidermal growth factor receptor) inhibitor, in patients with advanced non\u2013small cell lung cancer after failure of prior chemotherapy and erlotinib. Cancer. 2014;120:1145\u201354. https:\/\/doi.org\/10.1002\/cncr.28561.","journal-title":"Cancer"},{"key":"4331_CR77","doi-asserted-by":"publisher","first-page":"2252","DOI":"10.1200\/JCO.2005.01.8960","volume":"24","author":"C Erlichman","year":"2006","unstructured":"Erlichman C, Hidalgo M, Boni JP, Martins P, Quinn SE, Zacharchuk C, et al. Phase I Study of EKB-569, an irreversible inhibitor of the epidermal growth factor receptor, in patients with advanced solid tumors. J Clin Oncol. 2006;24:2252\u201360. https:\/\/doi.org\/10.1200\/JCO.2005.01.8960.","journal-title":"J Clin Oncol"},{"key":"4331_CR78","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1038\/s41392-021-00572-w","volume":"6","author":"L Zhong","year":"2021","unstructured":"Zhong L, Li Y, Xiong L, Wang W, Wu M, Yuan T, et al. Small molecules in targeted cancer therapy: advances, challenges, and future perspectives. Signal Transduct Target Ther. 2021;6:201. https:\/\/doi.org\/10.1038\/s41392-021-00572-w.","journal-title":"Signal Transduct Target Ther"},{"key":"4331_CR79","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/s41392-023-01469-6","volume":"8","author":"S Shyam Sunder","year":"2023","unstructured":"Shyam Sunder S, Sharma UC, Pokharel S. Adverse effects of tyrosine kinase inhibitors in cancer therapy: pathophysiology, mechanisms and clinical management. Signal Transduct Target Ther. 2023;8:262. https:\/\/doi.org\/10.1038\/s41392-023-01469-6.","journal-title":"Signal Transduct Target Ther"},{"key":"4331_CR80","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1021\/cb500886n","volume":"10","author":"O Hantschel","year":"2015","unstructured":"Hantschel O. Unexpected off-targets and paradoxical pathway activation by kinase inhibitors. ACS Chem Biol. 2015;10:234\u201345. https:\/\/doi.org\/10.1021\/cb500886n.","journal-title":"ACS Chem Biol"},{"key":"4331_CR81","doi-asserted-by":"publisher","first-page":"114","DOI":"10.3892\/etm.2021.11037","volume":"23","author":"G Iancu","year":"2021","unstructured":"Iancu G, Serban D, Badiu C, Tanasescu C, Tudosie M, Tudor C, et al. Tyrosine kinase inhibitors in breast cancer (review). Exp Ther Med. 2021;23:114. https:\/\/doi.org\/10.3892\/etm.2021.11037.","journal-title":"Exp Ther Med"},{"key":"4331_CR82","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1007\/s11864-023-01137-5","volume":"24","author":"M Stanowicka-Grada","year":"2023","unstructured":"Stanowicka-Grada M, Senkus E. Anti-HER2 drugs for the treatment of advanced HER2 positive breast cancer. Curr Treat Options Oncol. 2023;24:1633\u201350. https:\/\/doi.org\/10.1007\/s11864-023-01137-5.","journal-title":"Curr Treat Options Oncol"},{"key":"4331_CR83","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.70404","author":"MA Samad","year":"2025","unstructured":"Samad MA, Ahmad I, Khan MR, Suhail M, Zughaibi TA, Al\u2010Abbasi FA, et al. Breast cancer: molecular pathogenesis and targeted therapy. MedComm (Beijing). 2025. https:\/\/doi.org\/10.1002\/mco2.70404.","journal-title":"MedComm (Beijing)"},{"key":"4331_CR84","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1200\/JCO.2015.62.1797","volume":"34","author":"M Piccart-Gebhart","year":"2016","unstructured":"Piccart-Gebhart M, Holmes E, Baselga J, de Azambuja E, Dueck AC, Viale G, et al. Adjuvant Lapatinib and Trastuzumab for early human epidermal growth factor receptor 2\u2013positive breast cancer: results from the randomized phase III adjuvant Lapatinib and\/or Trastuzumab treatment optimization trial. J Clin Oncol. 2016;34:1034\u201342. https:\/\/doi.org\/10.1200\/JCO.2015.62.1797.","journal-title":"J Clin Oncol"},{"key":"4331_CR85","doi-asserted-by":"publisher","first-page":"736","DOI":"10.5498\/wjp.v11.i10.736","volume":"11","author":"X-Q Li","year":"2021","unstructured":"Li X-Q, Tang X-R, Li L-L. Antipsychotics cardiotoxicity: What\u2019s known and what\u2019s next. World J Psychiatry. 2021;11:736\u201353. https:\/\/doi.org\/10.5498\/wjp.v11.i10.736.","journal-title":"World J Psychiatry"},{"key":"4331_CR86","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1016\/j.annonc.2020.05.012","volume":"31","author":"CH Barcenas","year":"2020","unstructured":"Barcenas CH, Hurvitz SA, Di Palma JA, Bose R, Chien AJ, Iannotti N, et al. Improved tolerability of neratinib in patients with HER2-positive early-stage breast cancer: the CONTROL trial. Ann Oncol. 2020;31:1223\u201330. https:\/\/doi.org\/10.1016\/j.annonc.2020.05.012.","journal-title":"Ann Oncol"},{"key":"4331_CR87","doi-asserted-by":"publisher","first-page":"8352","DOI":"10.1002\/cam4.4335","volume":"10","author":"C Li","year":"2021","unstructured":"Li C, Bian X, Liu Z, Wang X, Song X, Zhao W, et al. Effectiveness and safety of Pyrotinib-based therapy in patients with HER2-positive metastatic breast cancer: a real-world retrospective study. Cancer Med. 2021;10:8352\u201364. https:\/\/doi.org\/10.1002\/cam4.4335.","journal-title":"Cancer Med"},{"key":"4331_CR88","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1056\/NEJMoa0810699","volume":"361","author":"TS Mok","year":"2009","unstructured":"Mok TS, Wu Y-L, Thongprasert S, Yang C-H, Chu D-T, Saijo N, et al. Gefitinib or carboplatin\u2013paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947\u201357. https:\/\/doi.org\/10.1056\/NEJMoa0810699.","journal-title":"N Engl J Med"},{"key":"4331_CR89","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1056\/NEJMoa1914609","volume":"382","author":"RK Murthy","year":"2020","unstructured":"Murthy RK, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz SA, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382:597\u2013609. https:\/\/doi.org\/10.1056\/NEJMoa1914609.","journal-title":"N Engl J Med"},{"key":"4331_CR90","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/j.jtho.2015.11.014","volume":"11","author":"M Schuler","year":"2016","unstructured":"Schuler M, Wu Y-L, Hirsh V, O\u2019Byrne K, Yamamoto N, Mok T, et al. First-line afatinib versus chemotherapy in patients with non\u2013small cell lung cancer and common Epidermal Growth Factor Receptor gene mutations and brain metastases. J Thorac Oncol. 2016;11:380\u201390. https:\/\/doi.org\/10.1016\/j.jtho.2015.11.014.","journal-title":"J Thorac Oncol"},{"key":"4331_CR91","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1158\/1078-0432.CCR-06-1539","volume":"13","author":"PN Munster","year":"2007","unstructured":"Munster PN, Britten CD, Mita M, Gelmon K, Minton SE, Moulder S, et al. First study of the safety, tolerability, and pharmacokinetics of CP-724,714 in patients with advanced malignant solid HER2-expressing tumors. Clin Cancer Res. 2007;13:1238\u201345. https:\/\/doi.org\/10.1158\/1078-0432.CCR-06-1539.","journal-title":"Clin Cancer Res"},{"key":"4331_CR92","doi-asserted-by":"publisher","DOI":"10.1186\/s13058-018-0990-2","volume":"20","author":"S Donzelli","year":"2018","unstructured":"Donzelli S, Milano E, Pruszko M, Sacconi A, Masciarelli S, Iosue I, et al. Expression of ID4 protein in breast cancer cells induces reprogramming of tumour-associated macrophages. Breast Cancer Res. 2018;20:59. https:\/\/doi.org\/10.1186\/s13058-018-0990-2.","journal-title":"Breast Cancer Res"},{"key":"4331_CR93","doi-asserted-by":"publisher","first-page":"13","DOI":"10.21037\/tbcr-20-25","volume":"1","author":"M Yan","year":"2020","unstructured":"Yan M, Bian L, Hu X, Zhang Q, Ouyang Q, Feng J, et al. Pyrotinib plus Capecitabine for human epidermal growth factor receptor 2-positive metastatic breast cancer after Trastuzumab and taxanes (PHENIX): a randomized, double-blind, placebo-controlled phase 3 study. Transl Breast Cancer Res. 2020;1:13\u201313. https:\/\/doi.org\/10.21037\/tbcr-20-25.","journal-title":"Transl Breast Cancer Res"},{"key":"4331_CR94","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12061573","volume":"12","author":"E Mezni","year":"2020","unstructured":"Mezni E, Vicier C, Guerin M, Sabatier R, Bertucci F, Gon\u00e7alves A. New therapeutics in HER2-positive advanced breast cancer: towards a change in clinical practices? Cancers (Basel). 2020;12:1573. https:\/\/doi.org\/10.3390\/cancers12061573.","journal-title":"Cancers (Basel)"},{"key":"4331_CR95","doi-asserted-by":"publisher","first-page":"2646","DOI":"10.1002\/adfm.201404629","volume":"25","author":"W Ngamcherdtrakul","year":"2015","unstructured":"Ngamcherdtrakul W, Morry J, Gu S, Castro DJ, Goodyear SM, Sangvanich T, et al. Cationic polymer modified mesoporous silica nanoparticles for targeted siRNA delivery to HER2 + breast cancer. Adv Funct Mater. 2015;25:2646\u201359. https:\/\/doi.org\/10.1002\/adfm.201404629.","journal-title":"Adv Funct Mater"},{"key":"4331_CR96","doi-asserted-by":"publisher","first-page":"181","DOI":"10.2147\/IJN.S219042","volume":"15","author":"M Khoobchandani","year":"2020","unstructured":"Khoobchandani M, Katti KK, Karikachery AR, Thipe VC, Srisrimal D, Dhurvas Mohandoss DK, et al. <p>New approaches in breast cancer therapy through green nanotechnology and nano-ayurvedic medicine \u2013 pre-clinical and pilot human clinical investigations<\/p>. Int J Nanomedicine. 2020;15:181\u201397. https:\/\/doi.org\/10.2147\/IJN.S219042.","journal-title":"Int J Nanomedicine"},{"key":"4331_CR97","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-24968-x","volume":"8","author":"M Truffi","year":"2018","unstructured":"Truffi M, Colombo M, Sorrentino L, Pandolfi L, Mazzucchelli S, Pappalardo F, et al. Multivalent exposure of Trastuzumab on iron oxide nanoparticles improves antitumor potential and reduces resistance in HER2-positive breast cancer cells. Sci Rep. 2018;8:6563. https:\/\/doi.org\/10.1038\/s41598-018-24968-x.","journal-title":"Sci Rep"},{"key":"4331_CR98","doi-asserted-by":"publisher","DOI":"10.3390\/nano9121793","volume":"9","author":"E Niza","year":"2019","unstructured":"Niza E, Noblejas-L\u00f3pez MdelM, Bravo I, Nieto-Jim\u00e9nez C, Castro-Osma JA, Canales-V\u00e1zquez J, et al. Trastuzumab-targeted biodegradable nanoparticles for enhanced delivery of Dasatinib in HER2+ metastasic breast cancer. Nanomaterials. 2019;9:1793. https:\/\/doi.org\/10.3390\/nano9121793.","journal-title":"Nanomaterials"},{"key":"4331_CR99","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.6004\/jnccn.2015.0131","volume":"13","author":"NE Ben-Baruch","year":"2015","unstructured":"Ben-Baruch NE, Bose R, Kavuri SM, Ma CX, Ellis MJ. HER2-mutated breast cancer responds to treatment with single-agent Neratinib, a second-generation HER2\/EGFR tyrosine kinase inhibitor. J Natl Compr Canc Netw. 2015;13:1061\u20134. https:\/\/doi.org\/10.6004\/jnccn.2015.0131.","journal-title":"J Natl Compr Canc Netw"},{"key":"4331_CR100","doi-asserted-by":"publisher","first-page":"e69","DOI":"10.1016\/j.clbc.2015.11.001","volume":"16","author":"MD Friedman","year":"2016","unstructured":"Friedman MD, Lacouture M, Dang C. Dermatologic adverse events associated with use of adjuvant Lapatinib in combination with Paclitaxel and Trastuzumab for HER2-positive breast cancer: a case series analysis. Clin Breast Cancer. 2016;16:e69-74. https:\/\/doi.org\/10.1016\/j.clbc.2015.11.001.","journal-title":"Clin Breast Cancer"},{"key":"4331_CR101","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1158\/1535-7163.MCT-19-0873","volume":"19","author":"A Kulukian","year":"2020","unstructured":"Kulukian A, Lee P, Taylor J, Rosler R, de Vries P, Watson D, et al. Preclinical activity of HER2-selective tyrosine kinase inhibitor Tucatinib as a single agent or in combination with Trastuzumab or Docetaxel in solid tumor models. Mol Cancer Ther. 2020;19:976\u201387. https:\/\/doi.org\/10.1158\/1535-7163.MCT-19-0873.","journal-title":"Mol Cancer Ther"}],"container-title":["Clinical and Translational Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12094-026-04331-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12094-026-04331-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12094-026-04331-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T03:10:23Z","timestamp":1787541023000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12094-026-04331-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,31]]},"references-count":101,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["4331"],"URL":"https:\/\/doi.org\/10.1007\/s12094-026-04331-7","relation":{},"ISSN":["1699-3055"],"issn-type":[{"value":"1699-3055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,31]]},"assertion":[{"value":"12 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 April 2026","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The original online version of this article was revised to correct the affiliation for author, Pranjal P. Gujarathi.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This article is a review of previously published literature and does not contain any new studies with human participants or animals performed by any of the authors. Therefore, ethical approval and consent to participate were not required.","order":2,"name":"Ethics","label":"Ethical approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Informed consent is not applicable for this review paper.","order":3,"name":"Ethics","label":"Informed consent","group":{"name":"EthicsHeading","label":"Declarations"}}]}}