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Current Updates on Trastuzumab Resistance in HER2 Overexpressing Breast Cancers

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Breast Cancer Metastasis and Drug Resistance

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1152))

Abstract

Trastuzumab represents the predominant therapy to target breast cancer subtype marked by HER2 amplification. It has been in use for two decades and its continued importance is underlined by recent FDA approvals of its biosimilar and conjugated versions. Progression to an aggressive disease with acquisition of resistance to trastuzumab remains a major clinical concern. In addition to a number of cellular signaling pathways being investigated, focus in recent years has also shifted to epigenetic and non-coding RNA basis of acquired resistance against trastuzumab. This article provides a succinct discussion on the most recent advances in our understanding of such factors.

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References

  1. Coussens L, Yang-Feng TL, Liao YC, Chen E, Gray A, McGrath J, Seeburg PH, Libermann TA, Schlessinger J, Francke U (1985) Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science 230:1132–1139

    Article  CAS  PubMed  Google Scholar 

  2. Ahmad A, Sarkar FH (2012) Current understanding of drug resistance mechanisms and therapeutic targets in HER2 overexpressing breast cancers. In: Ahmad A (ed) Breast cancer metastasis and drug resistance. Springer, Place Published, New York, pp 261–274

    Google Scholar 

  3. Stern DF, Heffernan PA, Weinberg RA (1986) p185, a product of the neu proto-oncogene, is a receptorlike protein associated with tyrosine kinase activity. Mol Cell Biol 6:1729–1740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182

    Article  CAS  PubMed  Google Scholar 

  5. Browne BC, O’Brien N, Duffy MJ, Crown J, O’Donovan N (2009) HER-2 signaling and inhibition in breast cancer. Curr Cancer Drug Targets 9:419–438

    Article  CAS  PubMed  Google Scholar 

  6. Vu T, Claret FX (2012) Trastuzumab: updated mechanisms of action and resistance in breast cancer. Front Oncol 2:62

    Article  PubMed  PubMed Central  Google Scholar 

  7. Narayan M, Wilken JA, Harris LN, Baron AT, Kimbler KD, Maihle NJ (2009) Trastuzumab-induced HER reprogramming in “resistant” breast carcinoma cells. Cancer Res 69:2191–2194

    Article  CAS  PubMed  Google Scholar 

  8. Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, De Van Vijver, Wheeler TM, Hayes DF (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25:118–145

    Article  CAS  PubMed  Google Scholar 

  9. Gajria D, Chandarlapaty S (2011) HER2-amplified breast cancer: mechanisms of trastuzumab resistance and novel targeted therapies. Expert Rev Anticancer Ther 11:263–275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Nahta R, Shabaya S, Ozbay T, Rowe DL (2009) Personalizing HER2-targeted therapy in metastatic breast cancer beyond HER2 status: what we have learned from clinical specimens. Curr Pharmacogenomics Person Med 7:263–274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Gallardo A, Lerma E, Escuin D, Tibau A, Munoz J, Ojeda B, Barnadas A, Adrover E, Sanchez-Tejada L, Giner D, Ortiz-Martinez F, Peiro G (2012) Increased signalling of EGFR and IGF1R, and deregulation of PTEN/PI3K/Akt pathway are related with trastuzumab resistance in HER2 breast carcinomas. Br J Cancer 106:1367–1373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zhang S, Huang WC, Li P, Guo H, Poh SB, Brady SW, Xiong Y, Tseng LM, Li SH, Ding Z, Sahin AA, Esteva FJ, Hortobagyi GN, Yu D (2011) Combating trastuzumab resistance by targeting SRC, a common node downstream of multiple resistance pathways. Nat Med 17:461–469

    Article  PubMed  Google Scholar 

  13. Elster N, Toomey S, Fan Y, Cremona M, Morgan C, Weiner Gorzel K, Bhreathnach U, Milewska M, Murphy M, Madden S, Naidoo J, Fay J, Kay E, Carr A, Kennedy S, Furney S, Mezynski J, Breathhnach O, Morris P, Grogan L, Hill A, Kennedy S, Crown J, Gallagher W, Hennessy B, Eustace A (2018) Frequency, impact and a preclinical study of novel ERBB gene family mutations in HER2-positive breast cancer. Therapeutic advances in medical oncology 10:1758835918778297

    Article  PubMed  PubMed Central  Google Scholar 

  14. Yang L, Li Y, Shen E, Cao F, Li L, Li X, Wang X, Kariminia S, Chang B, Li H, Li Q (2017) NRG1-dependent activation of HER3 induces primary resistance to trastuzumab in HER2-overexpressing breast cancer cells. Int J Oncol 51:1553–1562

    Article  CAS  PubMed  Google Scholar 

  15. Adamczyk A, Kruczak A, Harazin-Lechowska A, Ambicka A, Grela-Wojewoda A, Domagala-Haduch M, Janecka-Widla A, Majchrzyk K, Cichocka A, Rys J, Niemiec J (2018) Relationship between HER2 gene status and selected potential biological features related to trastuzumab resistance and its influence on survival of breast cancer patients undergoing trastuzumab adjuvant treatment. OncoTargets Ther 11:4525–4535

    Article  Google Scholar 

  16. Lyu H, Huang J, He Z, Liu B (2018) Targeting of HER3 with functional cooperative miRNAs enhances therapeutic activity in HER2-overexpressing breast cancer cells. Biological Proced Online 20:16

    Article  Google Scholar 

  17. Canfield K, Li J, Wilkins OM, Morrison MM, Ung M, Wells W, Williams CR, Liby KT, Vullhorst D, Buonanno A, Hu H, Schiff R, Cook RS, Kurokawa M (2015) Receptor tyrosine kinase ERBB4 mediates acquired resistance to ERBB2 inhibitors in breast cancer cells. Cell Cycle (Georgetown, Tex) 14:648–655

    Article  CAS  Google Scholar 

  18. Mohd Nafi SN, Generali D, Kramer-Marek G, Gijsen M, Strina C, Cappelletti M, Andreis D, Haider S, Li JL, Bridges E, Capala J, Ioannis R, Harris AL, Kong A (2014) Nuclear HER4 mediates acquired resistance to trastuzumab and is associated with poor outcome in HER2 positive breast cancer. Oncotarget 5:5934–5949

    PubMed  Google Scholar 

  19. Hanker AB, Garrett JT, Estrada MV, Moore PD, Ericsson PG, Koch JP, Langley E, Singh S, Kim PS, Frampton GM, Sanford E, Owens P, Becker J, Groseclose MR, Castellino S, Joensuu H, Huober J, Brase JC, Majjaj S, Brohee S, Venet D, Brown D, Baselga J, Piccart M, Sotiriou C, Arteaga CL (2017) HER2-overexpressing breast cancers amplify FGFR signaling upon acquisition of resistance to dual therapeutic blockade of HER2. Clin Cancer Res Off J Am Assoc Cancer Res 23:4323–4334

    Article  CAS  Google Scholar 

  20. Lenz G, Hamilton A, Geng S, Hong T, Kalkum M, Momand J, Kane SE, Huss JM (2018) T-Darpp activates IGF-1R signaling to regulate glucose metabolism in Trastuzumab-resistant breast cancer cells. Clin Cancer Res Off J Am Assoc Cancer Res 24:1216–1226

    Article  CAS  Google Scholar 

  21. Burnett JP, Korkaya H, Ouzounova MD, Jiang H, Conley SJ, Newman BW, Sun L, Connarn JN, Chen CS, Zhang N, Wicha MS, Sun D (2015) Trastuzumab resistance induces EMT to transform HER2(+) PTEN(−) to a triple negative breast cancer that requires unique treatment options. Sci Rep 5:15821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kim YJ, Sung D, Oh E, Cho Y, Cho TM, Farrand L, Seo JH, Kim JY (2018) Flubendazole overcomes trastuzumab resistance by targeting cancer stem-like properties and HER2 signaling in HER2-positive breast cancer. Cancer Lett 412:118–130

    Article  CAS  PubMed  Google Scholar 

  23. Chong QY, You ML, Pandey V, Banerjee A, Chen YJ, Poh HM, Zhang M, Ma L, Zhu T, Basappa S, Liu L, Lobie PE (2017) Release of HER2 repression of trefoil factor 3 (TFF3) expression mediates trastuzumab resistance in HER2+/ER+ mammary carcinoma. Oncotarget 8:74188–74208

    PubMed  PubMed Central  Google Scholar 

  24. Rodriguez CE, Berardi DE, Abrigo M, Todaro LB, Bal de Kier Joffe ED, Fiszman GL (2018) Breast cancer stem cells are involved in Trastuzumab resistance through the HER2 modulation in 3D culture. J Cell Biochem 119:1381–1391

    Article  CAS  PubMed  Google Scholar 

  25. Nami B, Wang Z (2017) HER2 in breast cancer stemness: a negative feedback loop towards Trastuzumab resistance. Cancers 9

    Google Scholar 

  26. De Cola A, Volpe S, Budani MC, Ferracin M, Lattanzio R, Turdo A, D’Agostino D, Capone E, Stassi G, Todaro M, Di Ilio C, Sala G, Piantelli M, Negrini M, Veronese A, De Laurenzi V (2015) miR-205-5p-mediated downregulation of ErbB/HER receptors in breast cancer stem cells results in targeted therapy resistance. Cell Death Dis 6:e1823

    Article  PubMed  PubMed Central  Google Scholar 

  27. Boulbes DR, Chauhan GB, Jin Q, Bartholomeusz C, Esteva FJ (2015) CD44 expression contributes to trastuzumab resistance in HER2-positive breast cancer cells. Breast Cancer Res Treat 151:501–513

    Article  CAS  PubMed  Google Scholar 

  28. van Rooijen JM, Qiu SQ, Timmer-Bosscha H, van der Vegt B, Boers JE, Schroder CP, de Vries EGE (2018) Androgen receptor expression inversely correlates with immune cell infiltration in human epidermal growth factor receptor 2-positive breast cancer. Eur J Cancer (Oxford, England: 1990) 103:52–60

    Article  Google Scholar 

  29. Martinez VG, O’Neill S, Salimu J, Breslin S, Clayton A, Crown J, O’Driscoll L (2017) Resistance to HER2-targeted anti-cancer drugs is associated with immune evasion in cancer cells and their derived extracellular vesicles. Oncoimmunology 6:e1362530

    Article  PubMed  PubMed Central  Google Scholar 

  30. Nunes J, Zhang H, Angelopoulos N, Chhetri J, Osipo C, Grothey A, Stebbing J, Giamas G (2016) ATG9A loss confers resistance to trastuzumab via c-Cbl mediated Her2 degradation. Oncotarget 7:27599–27612

    Article  PubMed  PubMed Central  Google Scholar 

  31. Xiong L, Ding L, Ning H, Wu C, Fu K, Wang Y, Zhang Y, Liu Y, Zhou L (2016) CD147 knockdown improves the antitumor efficacy of trastuzumab in HER2-positive breast cancer cells. Oncotarget 7:57737–57751

    PubMed  PubMed Central  Google Scholar 

  32. Kar A, Liu B, Gutierrez-Hartmann A (2017) ESE-1 knockdown attenuates growth in Trastuzumab-resistant HER2(+) breast cancer cells. Anticancer Res 37:6583–6591

    PubMed  PubMed Central  Google Scholar 

  33. Farahmand L, Merikhian P, Jalili N, Darvishi B, Majidzadeh AK (2018) Significant role of MUC1 in development of resistance to currently existing anti-cancer therapeutic agents. Curr Cancer Drug Targets 18:737–748

    Article  CAS  PubMed  Google Scholar 

  34. Mercogliano MF, De Martino M, Venturutti L, Rivas MA, Proietti CJ, Inurrigarro G, Frahm I, Allemand DH, Deza EG, Ares S, Gercovich FG, Guzman P, Roa JC, Elizalde PV, Schillaci R (2017) TNFalpha-induced mucin 4 expression elicits Trastuzumab resistance in HER2-positive breast cancer. Clin Cancer Res Off J Am Assoc Cancer Res 23:636–648

    Article  CAS  Google Scholar 

  35. Ding K, Wu Z, Li X, Sheng Y, Wang X, Tan S (2018) LMO4 mediates trastuzumab resistance in HER2 positive breast cancer cells. Am J Cancer Res 8:594–609

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Menyhart O, Budczies J, Munkacsy G, Esteva FJ, Szabo A, Miquel TP, Gyorffy B (2017) DUSP4 is associated with increased resistance against anti-HER2 therapy in breast cancer. Oncotarget 8:77207–77218

    Article  PubMed  PubMed Central  Google Scholar 

  37. Jin MH, Nam AR, Park JE, Bang JH, Bang YJ, Oh DY (2017) Resistance mechanism against Trastuzumab in HER2-positive cancer cells and its negation by Src inhibition. Mol Cancer Ther 16:1145–1154

    Article  CAS  PubMed  Google Scholar 

  38. Aghazadeh S, Yazdanparast R (2017) Activation of STAT3/HIF-1alpha/Hes-1 axis promotes trastuzumab resistance in HER2-overexpressing breast cancer cells via down-regulation of PTEN. Biochimic Biophys Acta Gen Subj 1861:1970–1980

    Article  CAS  Google Scholar 

  39. Sonnenblick A, Brohee S, Fumagalli D, Vincent D, Venet D, Ignatiadis M, Salgado R, Van den Eynden G, Rothe F, Desmedt C, Neven P, Loibl S, Denkert C, Joensuu H, Loi S, Sirtaine N, Kellokumpu-Lehtinen PL, Piccart M, Sotiriou C (2015) Constitutive phosphorylated STAT3-associated gene signature is predictive for trastuzumab resistance in primary HER2-positive breast cancer. BMC Med 13:177

    Article  PubMed  PubMed Central  Google Scholar 

  40. Chihara Y, Shimoda M, Hori A, Ohara A, Naoi Y, Ikeda JI, Kagara N, Tanei T, Shimomura A, Shimazu K, Kim SJ, Noguchi S (2017) A small-molecule inhibitor of SMAD3 attenuates resistance to anti-HER2 drugs in HER2-positive breast cancer cells. Breast Cancer Res Treat 166:55–68

    Article  CAS  PubMed  Google Scholar 

  41. Takeda T, Yamamoto H, Kanzaki H, Suzawa K, Yoshioka T, Tomida S, Cui X, Murali R, Namba K, Sato H, Torigoe H, Watanabe M, Shien K, Soh J, Asano H, Tsukuda K, Kitamura Y, Miyoshi S, Sendo T, Toyooka S (2017) Yes1 signaling mediates the resistance to Trastuzumab/lap atinib in breast cancer. PLoS One 12:e0171356

    Article  PubMed  PubMed Central  Google Scholar 

  42. Pandya K, Wyatt D, Gallagher B, Shah D, Baker A, Bloodworth J, Zlobin A, Pannuti A, Green A, Ellis IO, Filipovic A, Sagert J, Rana A, Albain KS, Miele L, Denning MF, Osipo C (2016) PKCalpha attenuates Jagged-1-mediated notch signaling in ErbB-2-positive breast cancer to reverse Trastuzumab resistance. Clin Cancer Res Off J Am Assoc Cancer Res 22:175–186

    Article  CAS  Google Scholar 

  43. Zhao B, Zhao Y, Sun Y, Niu H, Sheng L, Huang D, Li L (2018) Alterations in mRNA profiles of trastuzumabresistant Her2positive breast cancer. Mol Med Rep 18:139–146

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Liu W, Yuan J, Liu Z, Zhang J, Chang J (2018) Label-free quantitative proteomics combined with biological validation reveals activation of Wnt/beta-Catenin pathway contributing to Trastuzumab resistance in gastric cancer. Int J Mol Sci 19

    Article  PubMed Central  Google Scholar 

  45. Lee JY, Joo HS, Choi HJ, Jin S, Kim HY, Jeong GY, An HW, Park MK, Lee SE, Kim WS, Son T, Min KW, Oh YH, Kong G (2018) Role of MEL-18 amplification in anti-HER2 therapy of breast cancer. J Natl Cancer Inst

    Google Scholar 

  46. Mittal D, Caramia F, Michiels S, Joensuu H, Kellokumpu-Lehtinen PL, Sotiriou C, Loi S, Smyth MJ (2016) Improved treatment of breast cancer with anti-HER2 therapy requires Interleukin-21 signaling in CD8+ T cells. Cancer Res 76:264–274

    Article  CAS  PubMed  Google Scholar 

  47. Singla H, Ludhiadch A, Kaur RP, Chander H, Kumar V, Munshi A (2017) Recent advances in HER2 positive breast cancer epigenetics: susceptibility and therapeutic strategies. Eur J Med Chem 142:316–327

    Article  CAS  PubMed  Google Scholar 

  48. Dong H, Wang W, Mo S, Liu Q, Chen X, Chen R, Zhang Y, Zou K, Ye M, He X, Zhang F, Han J, Hu J (2018) Long non-coding RNA SNHG14 induces trastuzumab resistance of breast cancer via regulating PABPC1 expression through H3K27 acetylation. J Cell Mol Med 22:4935–4947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Fujii S, Yamashita S, Yamaguchi T, Takahashi M, Hozumi Y, Ushijima T, Mukai H (2017) Pathological complete response of HER2-positive breast cancer to trastuzumab and chemotherapy can be predicted by HSD17B4 methylation. Oncotarget 8:19039–19048

    PubMed  PubMed Central  Google Scholar 

  50. Ahmad A (2016) Non-coding RNAs: a tale of junk turning into treasure. Noncoding RNA Res 1:1–2

    Article  PubMed  Google Scholar 

  51. Campos-Parra AD, Lopez-Urrutia E, Orozco Moreno LT, Lopez-Camarillo C, Meza-Menchaca T, Figueroa Gonzalez G, Bustamante Montes LP, Perez-Plasencia C (2018) Long non-coding RNAs as new master regulators of resistance to systemic treatments in breast cancer. Int J Mol Sci 19

    Article  PubMed Central  Google Scholar 

  52. Zhu HY, Bai WD, Ye XM, Yang AG, Jia LT (2018) Long non-coding RNA UCA1 desensitizes breast cancer cells to trastuzumab by impeding miR-18a repression of Yes-associated protein 1. Biochem Biophys Res Commun 496:1308–1313

    Article  CAS  PubMed  Google Scholar 

  53. Shi SJ, Wang LJ, Yu B, Li YH, Jin Y, Bai XZ (2015) LncRNA-ATB promotes trastuzumab resistance and invasion-metastasis cascade in breast cancer. Oncotarget 6:11652–11663

    PubMed  PubMed Central  Google Scholar 

  54. Dong H, Wang W, Chen R, Zhang Y, Zou K, Ye M, He X, Zhang F, Han J (2018) Exosome-mediated transfer of lncRNASNHG14 promotes trastuzumab chemoresistance in breast cancer. Int J Oncol 53:1013–1026

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Li W, Zhai L, Wang H, Liu C, Zhang J, Chen W, Wei Q (2016) Downregulation of LncRNA GAS5 causes trastuzumab resistance in breast cancer. Oncotarget 7:27778–27786

    PubMed  PubMed Central  Google Scholar 

  56. De Mattos-Arruda L, Bottai G, Nuciforo PG, Di Tommaso L, Giovannetti E, Peg V, Losurdo A, Perez-Garcia J, Masci G, Corsi F, Cortes J, Seoane J, Calin GA, Santarpia L (2015) MicroRNA-21 links epithelial-to-mesenchymal transition and inflammatory signals to confer resistance to neoadjuvant trastuzumab and chemotherapy in HER2-positive breast cancer patients. Oncotarget 6:37269–37280

    PubMed  PubMed Central  Google Scholar 

  57. Sun C, Yang F, Zhang Y, Chu J, Wang J, Wang Y, Zhang Y, Li J, Li Y, Fan R, Li W, Huang X, Wu H, Fu Z, Jiang Z, Yin Y (2018) tRNA-derived fragments as novel predictive biomarkers for Trastuzumab-resistant breast cancer. Cell Physiol Biochem 49:419–431

    Article  CAS  PubMed  Google Scholar 

  58. Wang Z, Li Y, Ahmad A, Azmi AS, Kong D, Banerjee S, Sarkar FH (2010) Targeting miRNAs involved in cancer stem cell and EMT regulation: An emerging concept in overcoming drug resistance. Drug Resist Updat 13:109–118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Decker JT, Hall MS, Blaisdell RB, Schwark K, Jeruss JS, Shea LD (2018) Dynamic microRNA activity identifies therapeutic targets in trastuzumab-resistant HER2(+) breast cancer. Biotechnol Bioeng 115:2613–2623

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. von der Heyde S, Wagner S, Czerny A, Nietert M, Ludewig F, Salinas-Riester G, Arlt D, Beissbarth T (2015) mRNA profiling reveals determinants of trastuzumab efficiency in HER2-positive breast cancer. PLoS One 10:e0117818

    Article  PubMed  PubMed Central  Google Scholar 

  61. Lu X, Ma J, Chu J, Shao Q, Zhang Y, Lu G, Li J, Huang X, Li W, Li Y, Ling Y, Zhao T (2017) MiR-129-5p sensitizes the response of her-2 positive breast cancer to Trastuzumab by reducing Rps6. Cell Physiol Biochem 44:2346–2356

    Article  CAS  PubMed  Google Scholar 

  62. Ma T, Yang L, Zhang J (2015) MiRNA5423p downregulation promotes trastuzumab resistance in breast cancer cells via AKT activation. Oncol Rep 33:1215–1220

    Article  CAS  PubMed  Google Scholar 

  63. Huynh FC, Jones FE (2014) MicroRNA-7 inhibits multiple oncogenic pathways to suppress HER2Delta16 mediated breast tumorigenesis and reverse trastuzumab resistance. PLoS One 9:e114419

    Article  PubMed  PubMed Central  Google Scholar 

  64. Cataldo A, Piovan C, Plantamura I, D’Ippolito E, Camelliti S, Casalini P, Giussani M, Deas O, Cairo S, Judde JG, Tagliabue E, Iorio MV (2018) MiR-205 as predictive biomarker and adjuvant therapeutic tool in combination with trastuzumab. Oncotarget 9:27920–27928

    Article  PubMed  PubMed Central  Google Scholar 

  65. Li X, Xu Y, Ding Y, Li C, Zhao H, Wang J, Meng S (2018) Posttranscriptional upregulation of HER3 by HER2 mRNA induces trastuzumab resistance in breast cancer. Mol Cancer 17:113

    Article  PubMed  PubMed Central  Google Scholar 

  66. Yue D, Qin X (2018) miR-182 regulates trastuzumab resistance by targeting MET in breast cancer cells. Cancer Gene Ther 26(1–2):1–10

    PubMed  Google Scholar 

  67. Tormo E, Adam-Artigues A, Ballester S, Pineda B, Zazo S, Gonzalez-Alonso P, Albanell J, Rovira A, Rojo F, Lluch A, Eroles P (2017) The role of miR-26a and miR-30b in HER2+ breast cancer trastuzumab resistance and regulation of the CCNE2 gene. Sci Rep 7:41309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Venturutti L, Cordo Russo RI, Rivas MA, Mercogliano MF, Izzo F, Oakley RH, Pereyra MG, De Martino M, Proietti CJ, Yankilevich P, Roa JC, Guzman P, Cortese E, Allemand DH, Huang TH, Charreau EH, Cidlowski JA, Schillaci R, Elizalde PV (2016) MiR-16 mediates trastuzumab and lapatinib response in ErbB-2-positive breast and gastric cancer via its novel targets CCNJ and FUBP1. Oncogene 35:6189–6202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Li H, Liu J, Chen J, Wang H, Yang L, Chen F, Fan S, Wang J, Shao B, Yin D, Zeng M, Li M, Li J, Su F, Liu Q, Yao H, Su S, Song E (2018) A serum microRNA signature predicts trastuzumab benefit in HER2-positive metastatic breast cancer patients. Nat Commun 9:1614

    Article  PubMed  PubMed Central  Google Scholar 

  70. Soto-Perez-De-Celis E, Loh KP, Baldini C, Battisti NML, Chavarri-Guerra Y, De Glas NA, Hsu T, Hurria A (2018) Targeted agents for HER2-positive breast cancer in older adults: current and future perspectives. Expert Opin Investig Drugs 27:787–801

    Article  CAS  PubMed  Google Scholar 

  71. Wang L, Wang Q, Gao M, Fu L, Li Y, Quan H, Lou L (2018) STAT3 activation confers trastuzumab-emtansine (T-DM1) resistance in HER2-positive breast cancer. Cancer Sci 109:3305–3315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Sakai H, Tsurutani J, Iwasa T, Komoike Y, Sakai K, Nishio K, Nakagawa K (2018) HER2 genomic amplification in circulating tumor DNA and estrogen receptor positivity predict primary resistance to trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer. Breast Cancer (Tokyo, Japan) 25:605–613

    Article  Google Scholar 

  73. Li G, Guo J, Shen BQ, Yadav DB, Sliwkowski MX, Crocker LM, Lacap JA, Phillips GDL (2018) Mechanisms of acquired resistance to Trastuzumab Emtansine in breast cancer cells. Mol Cancer Ther 17:1441–1453

    Article  CAS  PubMed  Google Scholar 

  74. Mao Y, Zhang Y, Qu Q, Zhao M, Lou Y, Liu J, huang O, Chen X, Wu J, Shen K (2015) Cancer-associated fibroblasts induce trastuzumab resistance in HER2 positive breast cancer cells. Mol BioSyst 11:1029–1040

    Article  CAS  PubMed  Google Scholar 

  75. Tanioka M, Fan C, Parker JS, Hoadley KA, Hu Z, Li Y, Hyslop TM, Pitcher BN, Soloway MG, Spears PA, Henry LN, Tolaney S, Dang CT, Krop IE, Harris LN, Berry DA, Mardis ER, Winer EP, Hudis CA, Carey LA, Perou CM (2018) Integrated analysis of RNA and DNA from the phase III trial CALGB 40601 identifies predictors of response to Trastuzumab-based neoadjuvant chemotherapy in HER2-positive breast cancer. Clin Cancer Res Off J Am Assoc Cancer Res 24:5292–5304

    Article  Google Scholar 

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  1. Mitchell Cancer Institute, University of South Alabama, Mobile, AL, USA

    Aamir Ahmad

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    Aamir Ahmad

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Ahmad, A. (2019). Current Updates on Trastuzumab Resistance in HER2 Overexpressing Breast Cancers. In: Ahmad, A. (eds) Breast Cancer Metastasis and Drug Resistance. Advances in Experimental Medicine and Biology, vol 1152. Springer, Cham. https://doi.org/10.1007/978-3-030-20301-6_10

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