Trastuzumab emtansine: Mechanisms of action and drug resistance

Breast Cancer Research

Volumn 16, Issue 2, 2014, Pages

  Barok, Mark ^a   Joensuu, Heikki ^b   Isola, Jorma ^c  

^a UNIVERSITY OF HELSINKI   (Finland)

^b HELSINKI UNIVERSITY CENTRAL HOSPITAL   (Finland)

^c TAMPERE UNIVERSITY OF TECHNOLOGY   (Finland)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOTRANSFERASE; CAPECITABINE; DOCETAXEL; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR 3; EPITOPE; GELDANAMYCIN; IMMUNOGLOBULIN FC FRAGMENT; LAPATINIB; MULTIDRUG RESISTANCE PROTEIN 1; NEU DIFFERENTIATION FACTOR; NLS TRASTUZUMAB IN 11; PACLITAXEL; PERTUZUMAB; PICTILISIB; PLACEBO; RADIOPHARMACEUTICAL AGENT; TAXANE DERIVATIVE; TRASTUZUMAB; TRASTUZUMAB EMTANSINE; TUBULIN; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; ERBB2 PROTEIN, HUMAN; MAYTANSINE; MONOCLONAL ANTIBODY;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; BREAST METASTASIS; CANCER ADJUVANT THERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER RECURRENCE; CANCER RESISTANCE; CELL MIGRATION; CONCENTRATION RESPONSE; DRUG BINDING; DRUG CONJUGATION; DRUG CYTOTOXICITY; DRUG DEGRADATION; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; ENDOSOME; HUMAN; INTERNALIZATION; LYSOSOME; MITOSIS; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PROTEIN EXPRESSION; PROTEIN INTERACTION; RADIOIMMUNOTHERAPY; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; TARGET CELL; ADJUVANT CHEMOTHERAPY; ANALOGS AND DERIVATIVES; BREAST NEOPLASMS; DRUG EFFECTS; DRUG RESISTANCE; FEMALE; METABOLISM; PATHOLOGY; TREATMENT OUTCOME;

ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC AGENTS; APOPTOSIS; BREAST NEOPLASMS; CHEMOTHERAPY, ADJUVANT; DRUG RESISTANCE, NEOPLASM; FEMALE; HUMANS; MAYTANSINE; RECEPTOR, ERBB-2; TREATMENT OUTCOME;

EID: 84896776546     PISSN: 14655411     EISSN: 1465542X     Source Type: Journal    
DOI: 10.1186/bcr3621     Document Type: Review

References (82)

1. Pauletti G, Dandekar S, Rong H, Ramos L, Peng H, Seshadri R, Slamon DJ. Assessment of methods for tissue-based detection of the HER-2/neu alteration in human breast cancer: a direct comparison of fluorescence in situ hybridization and immunohistochemistry. J Clin Oncol 2000, 18:3651-3664.
2. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987, 235:177-182. 10.1126/science.3798106, 3798106.
3. Sliwkowski MX, Lofgren JA, Lewis GD, Hotaling TE, Fendly BM, Fox JA. Nonclinical studies addressing the mechanism of action of trastuzumab (Herceptin). Semin Oncol 1999, 26:60-70.
4. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001, 344:783-792. 10.1056/NEJM200103153441101, 11248153.
5. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M, Barrios CH, Steger G, Huang CS, Andersson M, Inbar M, Lichinitser M, Lang I, Nitz U, Iwata H, Thomssen C, Lohrisch C, Suter TM, Ruschoff J, Suto T, Greatorex V, Ward C, Straehle C, McFadden E, Dolci MS, Gelber R, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005, 353:1659-1672. 10.1056/NEJMoa052306, 16236737.
6. Nahta R, Yu D, Hung MC, Hortobagyi GN, Esteva FJ. Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer. Nat Clin Pract Oncol 2006, 3:269-280. 10.1038/ncponc0509, 16683005.
7. Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 2006, 355:2733-2743. 10.1056/NEJMoa064320, 17192538.
8. Nahta R, Shabaya S, Ozbay T, Rowe DL. Personalizing HER2-targeted therapy in metastatic breast cancer beyond HER2 status: what we have learned from clinical specimens. Curr Pharmacogenomics Person Med 2009, 7:263-274. 10.2174/187569209790112337, 2840656, 20300449.
9. Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 2012, 366:109-119. 10.1056/NEJMoa1113216, 22149875.
10. O'Neill GJ. The use of antibodies as drug carriers. Drug Carriers in Biology and Medicine 1979, 23-43. London: Academic Press, Gregoriadis G.
11. Lewis Phillips GD, Li G, Dugger DL, Crocker LM, Parsons KL, Mai E, Blattler WA, Lambert JM, Chari RV, Lutz RJ, Wong WL, Jacobson FS, Koeppen H, Schwall RH, Kenkare-Mitra SR, Spencer SD, Sliwkowski MX. Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res 2008, 68:9280-9290. 10.1158/0008-5472.CAN-08-1776, 19010901.
12. Kovtun YV, Goldmacher VS. Cell killing by antibody-drug conjugates. Cancer Lett 2007, 255:232-240. 10.1016/j.canlet.2007.04.010, 17553616.
13. Ritchie M, Tchistiakova L, Scott N. Implications of receptor-mediated endocytosis and intracellular trafficking dynamics in the development of antibody drug conjugates. MAbs 2013, 5:13-21. 10.4161/mabs.22854, 3564878, 23221464.
14. Erickson HK, Park PU, Widdison WC, Kovtun YV, Garrett LM, Hoffman K, Lutz RJ, Goldmacher VS, Blattler WA. Antibody-maytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing. Cancer Res 2006, 66:4426-4433. 10.1158/0008-5472.CAN-05-4489, 16618769.
15. Chari RV. Targeted cancer therapy: conferring specificity to cytotoxic drugs. Acc Chem Res 2008, 41:98-107. 10.1021/ar700108g, 17705444.
16. Junttila TT, Li G, Parsons K, Phillips GL, Sliwkowski MX. Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer. Breast Cancer Res Treat 2010, 128:347-356.
17. Barok M, Tanner M, Koninki K, Isola J. Trastuzumab-DM1 is highly effective in preclinical models of HER2-positive gastric cancer. Cancer Lett 2011, 306:171-179. 10.1016/j.canlet.2011.03.002, 21458915.
18. Barok M, Tanner M, Koninki K, Isola J. Trastuzumab-DM1 causes tumour growth inhibition by mitotic catastrophe in trastuzumab-resistant breast cancer cells in vivo. Breast Cancer Res 2011, 13:R46. 10.1186/bcr2868, 3219209, 21510863.
19. Cuello M, Ettenberg SA, Clark AS, Keane MM, Posner RH, Nau MM, Dennis PA, Lipkowitz S. Down-regulation of the erbB-2 receptor by trastuzumab (herceptin) enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in breast and ovarian cancer cell lines that overexpress erbB-2. Cancer Res 2001, 61:4892-4900.
20. Nagy P, Friedlander E, Tanner M, Kapanen AI, Carraway KL, Isola J, Jovin TM. Decreased accessibility and lack of activation of ErbB2 in JIMT-1, a herceptin-resistant, MUC4-expressing breast cancer cell line. Cancer Res 2005, 65:473-482.
21. Palyi-Krekk Z, Barok M, Isola J, Tammi M, Szollosi J, Nagy P. Hyaluronan-induced masking of ErbB2 and CD44-enhanced trastuzumab internalisation in trastuzumab resistant breast cancer. Eur J Cancer 2007, 43:2423-2433. 10.1016/j.ejca.2007.08.018, 17911008.
22. Molina MA, Codony-Servat J, Albanell J, Rojo F, Arribas J, Baselga J. Trastuzumab (herceptin), a humanized anti-Her2 receptor monoclonal antibody, inhibits basal and activated Her2 ectodomain cleavage in breast cancer cells. Cancer Res 2001, 61:4744-4749.
23. Arribas J, Baselga J, Pedersen K, Parra-Palau JL. p95HER2 and breast cancer. Cancer Res 2011, 71:1515-1519. 10.1158/0008-5472.CAN-10-3795, 21343397.
24. Kono K, Sato E, Naganuma H, Takahashi A, Mimura K, Nukui H, Fujii H. Trastuzumab (Herceptin) enhances class I-restricted antigen presentation recognized by HER-2/neu-specific T cytotoxic lymphocytes. Clin Cancer Res 2004, 10:2538-2544. 10.1158/1078-0432.CCR-03-0424, 15073134.
25. Lu Y, Zi X, Zhao Y, Mascarenhas D, Pollak M. Insulin-like growth factor-I receptor signaling and resistance to trastuzumab (Herceptin). J Natl Cancer Inst 2001, 93:1852-1857. 10.1093/jnci/93.24.1852, 11752009.
26. Nagata Y, Lan KH, Zhou X, Tan M, Esteva FJ, Sahin AA, Klos KS, Li P, Monia BP, Nguyen NT, Hortobagyi GN, Hung MC, Yu D. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell 2004, 6:117-127. 10.1016/j.ccr.2004.06.022, 15324695.
27. Scaltriti M, Eichhorn PJ, Cortes J, Prudkin L, Aura C, Jimenez J, Chandarlapaty S, Serra V, Prat A, Ibrahim YH, Guzman M, Gili M, Rodriguez O, Rodriguez S, Perez J, Green SR, Mai S, Rosen N, Hudis C, Baselga J. Cyclin E amplification/overexpression is a mechanism of trastuzumab resistance in HER2+ breast cancer patients. Proc Natl Acad Sci U S A 2011, 108:3761-3766. 10.1073/pnas.1014835108, 3048107, 21321214.
28. Izumi Y, Xu L, di Tomaso E, Fukumura D, Jain RK. Tumour biology: herceptin acts as an anti-angiogenic cocktail. Nature 2002, 416:279-280.
29. Motoyama AB, Hynes NE, Lane HA. The efficacy of ErbB receptor-targeted anticancer therapeutics is influenced by the availability of epidermal growth factor-related peptides. Cancer Res 2002, 62:3151-3158.
30. Barok M, Isola J, Palyi-Krekk Z, Nagy P, Juhasz I, Vereb G, Kauraniemi P, Kapanen A, Tanner M, Szollosi J. Trastuzumab causes antibody-dependent cellular cytotoxicity-mediated growth inhibition of submacroscopic JIMT-1 breast cancer xenografts despite intrinsic drug resistance. Mol Cancer Ther 2007, 6:2065-2072. 10.1158/1535-7163.MCT-06-0766, 17620435.
31. Kono K, Takahashi A, Ichihara F, Sugai H, Fujii H, Matsumoto Y. Impaired antibody-dependent cellular cytotoxicity mediated by herceptin in patients with gastric cancer. Cancer Res 2002, 62:5813-5817.
32. von Minckwitz G, du Bois A, Schmidt M, Maass N, Cufer T, de Jongh FE, Maartense E, Zielinski C, Kaufmann M, Bauer W, Baumann KH, Clemens MR, Duerr R, Uleer C, Andersson M, Stein RC, Nekljudova V, Loibl S. Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a german breast group 26/breast international group 03-05 study. J Clin Oncol 2009, 27:1999-2006. 10.1200/JCO.2008.19.6618, 19289619.
33. Blackwell KL, Burstein HJ, Storniolo AM, Rugo H, Sledge G, Koehler M, Ellis C, Casey M, Vukelja S, Bischoff J, Baselga J, O'Shaughnessy J. Randomized study of lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol 2010, 28:1124-1130. 10.1200/JCO.2008.21.4437, 20124187.
34. Komlodi-Pasztor E, Sackett D, Wilkerson J, Fojo T. Mitosis is not a key target of microtubule agents in patient tumors. Nat Rev Clin Oncol 2011, 8:244-250. 10.1038/nrclinonc.2010.228, 21283127.
35. Komlodi-Pasztor E, Sackett DL, Fojo AT. Inhibitors targeting mitosis: tales of how great drugs against a promising target were brought down by a flawed rationale. Clin Cancer Res 2012, 18:51-63. 10.1158/1078-0432.CCR-11-0999, 22215906.
36. Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Dieras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012, 367:1783-1791. 10.1056/NEJMoa1209124, 23020162.
37. Hurvitz SA, Dirix L, Kocsis J, Bianchi GV, Lu J, Vinholes J, Guardino E, Song C, Tong B, Ng V, Chu YW, Perez EA. Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol 2013, 31:1157-1163. 10.1200/JCO.2012.44.9694, 23382472.
38. Wildiers H, Kim SB, Gonzalez-Martin A, LoRusso PM, Ferrero JM, Smitt M, Yu R, Leung A, Krop IE. T-DM1 for HER2-positive metastatic breast cancer: primary results of TH3RESA, a phase 3 study of T-DM1 vs treatment of physician's choice [abstract LBA15]. Eur J Cancer 2013, S7-S8.
39. Tan X, Jin G, Myers J, Diesl V, Follettie M, Lam M-H, Musto S, Khandke K, Charati M, Graziani E, Maderna A, Subramanyam C, Koehn F, Dushin R, Arndt K, O'Donnell CJ, Gerber HP, Loganzo F. Tumor cells selected for resistance to an antibody-drug conjugate retain sensitivity to ADCs with modified linkers and payloads [abstract]. Cancer Res 2013, 73:Abstract 4629.
40. Li G, Fields CT, Parsons KL, Guo J, Lewis Phillips GD. Trastuzumab-DM1: mechanisms of action and mechanisms of resistance [abstract]. Eur J Cancer Supplements 2010, 8:73.
41. Burris HA, Rugo HS, Vukelja SJ, Vogel CL, Borson RA, Limentani S, Tan-Chiu E, Krop IE, Michaelson RA, Girish S, Amler L, Zheng M, Chu YW, Klencke B, O'Shaughnessy JA. Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after prior HER2-directed therapy. J Clin Oncol 2011, 29:398-405. 10.1200/JCO.2010.29.5865, 21172893.
42. LoRusso P, Krop IE, Burris HA, Vukelja SJ, Miller K, Zheng M, Chu Y, Lu M, Amler LC, Rugo HS. Quantitative assessment of diagnostic markers and correlations with efficacy in two phase II studies of trastuzumab-DM1 (T-DM1) for patients (pts) with metastatic breast cancer (MBC) who had progressed on prior HER2-directed therapy [abstract 1016]. J Clin Oncol 2010, 28:15 s.
43. LoRusso PM, Weiss D, Guardino E, Girish S, Sliwkowski MX. Trastuzumab emtansine: a unique antibody-drug conjugate in development for human epidermal growth factor receptor 2-positive cancer. Clin Cancer Res 2011, 17:6437-6447. 10.1158/1078-0432.CCR-11-0762, 22003071.
44. Lower EE, Glass E, Blau R, Harman S. HER-2/neu expression in primary and metastatic breast cancer. Breast Cancer Res Treat 2009, 113:301-306. 10.1007/s10549-008-9931-6, 18273700.
45. Niikura N, Liu J, Hayashi N, Mittendorf EA, Gong Y, Palla SL, Tokuda Y, Gonzalez-Angulo AM, Hortobagyi GN, Ueno NT. Loss of human epidermal growth factor receptor 2 (HER2) expression in metastatic sites of HER2-overexpressing primary breast tumors. J Clin Oncol 2012, 30:593-599. 10.1200/JCO.2010.33.8889, 3295557, 22124109.
46. Lee GH, Kim DS, Kim HT, Lee JW, Chung CH, Ahn T, Lim JM, Kim IK, Chae HJ, Kim HR. Enhanced lysosomal activity is involved in Bax inhibitor-1-induced regulation of the endoplasmic reticulum (ER) stress response and cell death against ER stress: involvement of vacuolar H + -ATPase (V-ATPase). J Biol Chem 2011, 286:24743-24753. 10.1074/jbc.M110.167734, 3137050, 21586565.
47. Dornan D, Settleman J. Predictive biomarkers for antibody-drug conjugates. Antibody-Drug Conjugates and Immunotoxins, From Pre-Clinical Development to Therapeutic Application 2013, 77-92. New York: Humana Press, Lewis Phillips GD.
48. Liddil JD, Dorr RT, Scuderi P. Association of lysosomal activity with sensitivity and resistance to tumor necrosis factor in murine L929 cells. Cancer Res 1989, 49:2722-2728.
49. Von Schwarzenberg K, Lajtos T, Simon L, Muller R, Vereb G, Vollmar AM. V-ATPase inhibition overcomes trastuzumab resistance in breast cancer. Mol Oncol 2013, in press.
50. Austin CD, De Maziere AM, Pisacane PI, van Dijk SM, Eigenbrot C, Sliwkowski MX, Klumperman J, Scheller RH. Endocytosis and sorting of ErbB2 and the site of action of cancer therapeutics trastuzumab and geldanamycin. Mol Biol Cell 2004, 15:5268-5282. 10.1091/mbc.E04-07-0591, 532009, 15385631.
51. Leonard GD, Fojo T, Bates SE. The role of ABC transporters in clinical practice. Oncologist 2003, 8:411-424. 10.1634/theoncologist.8-5-411, 14530494.
52. Takara K, Sakaeda T, Okumura K. An update on overcoming MDR1-mediated multidrug resistance in cancer chemotherapy. Curr Pharm Des 2006, 12:273-286. 10.2174/138161206775201965, 16454744.
53. Kovtun YV, Audette CA, Mayo MF, Jones GE, Doherty H, Maloney EK, Erickson HK, Sun X, Wilhelm S, Ab O, Lai KC, Widdison WC, Kellogg B, Johnson H, Pinkas J, Lutz RJ, Singh R, Goldmacher VS, Chari RV. Antibody-maytansinoid conjugates designed to bypass multidrug resistance. Cancer Res 2010, 70:2528-2537. 10.1158/0008-5472.CAN-09-3546, 20197459.
54. Lewis Phillips GD, Fields CT, Li G, Dowbenko D, Schaefer G, Miller K, Andre F, Burris HA, Albain KS, Harbeck N, Dieras V, Crivellari D, Fang L, Guardino E, Olsen SR, Crocker LM, Sliwkowski MX. Dual targeting of HER2-positive cancer with trastuzumab emtansine and pertuzumab: critical role for neuregulin blockade in antitumor response to combination therapy. Clin Cancer Res 2014, 20:456-468. 10.1158/1078-0432.CCR-13-0358, 24097864.
55. Barbareschi M, Cuorvo LV, Girlando S, Bragantini E, Eccher C, Leonardi E, Ferro A, Caldara A, Triolo R, Cantaloni C, Decarli N, Galligioni E, Dalla Palma P. PI3KCA mutations and/or PTEN loss in Her2-positive breast carcinomas treated with trastuzumab are not related to resistance to anti-Her2 therapy. Virchows Arch 2012, 461:129-139. 10.1007/s00428-012-1267-2, 22744290.
56. Loi S, Michiels S, Lambrechts D, Fumagalli D, Claes B, Kellokumpu-Lehtinen PL, Bono P, Kataja V, Piccart MJ, Joensuu H, Sotiriou C. Somatic mutation profiling and associations with prognosis and trastuzumab benefit in early breast cancer. J Natl Cancer Inst 2013, 105:960-967. 10.1093/jnci/djt121, 23739063.
57. Perez EA, Dueck AC, McCullough AE, Chen B, Geiger XJ, Jenkins RB, Lingle WL, Davidson NE, Martino S, Kaufman PA, Kutteh LA, Sledge GW, Harris LN, Gralow JR, Reinholz MM. Impact of PTEN protein expression on benefit from adjuvant trastuzumab in early-stage human epidermal growth factor receptor 2-positive breast cancer in the North Central Cancer Treatment Group N9831 trial. J Clin Oncol 2013, 31:2115-2122. 10.1200/JCO.2012.42.2642, 23650412.
58. Cabral F, Sobel ME, Gottesman MM. CHO mutants resistant to colchicine, colcemid or griseofulvin have an altered beta-tubulin. Cell 1980, 20:29-36. 10.1016/0092-8674(80)90231-7, 7388944.
59. Kavallaris M. Microtubules and resistance to tubulin-binding agents. Nat Rev Cancer 2010, 10:194-204. 10.1038/nrc2803, 20147901.
60. Morse DL, Gray H, Payne CM, Gillies RJ. Docetaxel induces cell death through mitotic catastrophe in human breast cancer cells. Mol Cancer Ther 2005, 4:1495-1504. 10.1158/1535-7163.MCT-05-0130, 16227398.
61. Torres K, Horwitz SB. Mechanisms of Taxol-induced cell death are concentration dependent. Cancer Res 1998, 58:3620-3626.
62. Hernandez-Vargas H, Palacios J, Moreno-Bueno G. Molecular profiling of docetaxel cytotoxicity in breast cancer cells: uncoupling of aberrant mitosis and apoptosis. Oncogene 2007, 26:2902-2913. 10.1038/sj.onc.1210102, 17099726.
63. Vakifahmetoglu H, Olsson M, Zhivotovsky B. Death through a tragedy: mitotic catastrophe. Cell Death Differ 2008, 15:1153-1162. 10.1038/cdd.2008.47, 18404154.
64. ClinicalTrials.gov. [http://clinicaltrials.gov].
65. Mohsin SK, Weiss HL, Gutierrez MC, Chamness GC, Schiff R, Digiovanna MP, Wang CX, Hilsenbeck SG, Osborne CK, Allred DC, Elledge R, Chang JC. Neoadjuvant trastuzumab induces apoptosis in primary breast cancers. J Clin Oncol 2005, 23:2460-2468. 10.1200/JCO.2005.00.661, 15710948.
66. Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, Chan S, Grimes D, Anton A, Lluch A, Kennedy J, O'Byrne K, Conte P, Green M, Ward C, Mayne K, Extra JM. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol 2005, 23:4265-4274. 10.1200/JCO.2005.04.173, 15911866.
67. Bhattacharyya B, Wolff J. Maytansine binding to the vinblastine sites of tubulin. FEBS Lett 1977, 75:159-162. 10.1016/0014-5793(77)80075-6, 852577.
68. Schaller G, Fuchs I, Gonsch T, Weber J, Kleine-Tebbe A, Klare P, Hindenburg HJ, Lakner V, Hinke A, Bangemann N. Phase II study of capecitabine plus trastuzumab in human epidermal growth factor receptor 2 overexpressing metastatic breast cancer pretreated with anthracyclines or taxanes. J Clin Oncol 2007, 25:3246-3250. 10.1200/JCO.2006.09.6826, 17577021.
69. Wardley AM, Pivot X, Morales-Vasquez F, Zetina LM, de Fatima Dias Gaui M, Reyes DO, Jassem J, Barton C, Button P, Hersberger V, Torres AA. Randomized phase II trial of first-line trastuzumab plus docetaxel and capecitabine compared with trastuzumab plus docetaxel in HER2-positive metastatic breast cancer. J Clin Oncol 2010, 28:976-983. 10.1200/JCO.2008.21.6531, 20038734.
70. Swain SM, Kim SB, Cortes J, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Knott A, Clark E, Ross G, Benyunes MC, Baselga J. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol 2013, 14:461-471. 10.1016/S1470-2045(13)70130-X, 23602601.
71. Blackwell KL, Burstein HJ, Storniolo AM, Rugo HS, Sledge G, Aktan G, Ellis C, Florance A, Vukelja S, Bischoff J, Baselga J, O'Shaughnessy J. Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EGF104900 Study. J Clin Oncol 2012, 30:2585-2592. 10.1200/JCO.2011.35.6725, 22689807.
72. Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Revil C, Jones A. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol 2009, 27:5529-5537. 10.1200/JCO.2008.20.6847, 19786670.
73. Huober J, Fasching PA, Barsoum M, Petruzelka L, Wallwiener D, Thomssen C, Reimer T, Paepke S, Azim HA, Ragosch V, Kubista E, Baumgartner AK, Beckmann MW, May C, Nimmrich I, Harbeck N. Higher efficacy of letrozole in combination with trastuzumab compared to letrozole monotherapy as first-line treatment in patients with HER2-positive, hormone-receptor-positive metastatic breast cancer - results of the eLEcTRA trial. Breast 2012, 21:27-33. 10.1016/j.breast.2011.07.006, 21862331.
74. Yao E, Zhou W, Lee-Hoeflich ST, Truong T, Haverty PM, Eastham-Anderson J, Lewin-Koh N, Gunter B, Belvin M, Murray LJ, Friedman LS, Sliwkowski MX, Hoeflich KP. Suppression of HER2/HER3-mediated growth of breast cancer cells with combinations of GDC-0941 PI3K inhibitor, trastuzumab, and pertuzumab. Clin Cancer Res 2009, 15:4147-4156. 10.1158/1078-0432.CCR-08-2814, 19509167.
75. Junttila TT, Akita RW, Parsons K, Fields C, Lewis Phillips GD, Friedman LS, Sampath D, Sliwkowski MX. Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer Cell 2009, 15:429-440. 10.1016/j.ccr.2009.03.020, 19411071.
76. Tikhomirov O, Carpenter G. Geldanamycin induces ErbB-2 degradation by proteolytic fragmentation. J Biol Chem 2000, 275:26625-26631. 10.1074/jbc.M003114200, 10862618.
77. Isaacs JS, Xu W, Neckers L. Heat shock protein 90 as a molecular target for cancer therapeutics. Cancer Cell 2003, 3:213-217. 10.1016/S1535-6108(03)00029-1, 12676580.
78. Khandelwal A, Saber H, Shapiro MA, Zhao H. Antibody-drug conjugate development. Antibody-Drug Conjugates and Immunotoxins, From Pre-Clinical Development to Therapeutic Application 2013, 23-40. New York: Humana Press, Lewis Phillips GD.
79. Hamblett KJ, Senter PD, Chace DF, Sun MM, Lenox J, Cerveny CG, Kissler KM, Bernhardt SX, Kopcha AK, Zabinski RF, Meyer DL, Francisco JA. Effects of drug loading on the antitumor activity of a monoclonal antibody drug conjugate. Clin Cancer Res 2004, 10:7063-7070. 10.1158/1078-0432.CCR-04-0789, 15501986.
80. Junttila TT, Parsons K, Olsson C, Lu Y, Xin Y, Theriault J, Crocker L, Pabonan O, Baginski T, Meng G, Totpal K, Kelley RF, Sliwkowski MX. Superior in vivo efficacy of afucosylated trastuzumab in the treatment of HER2-amplified breast cancer. Cancer Res 2010, 70:4481-4489. 10.1158/0008-5472.CAN-09-3704, 20484044.
81. Lazar GA, Dang W, Karki S, Vafa O, Peng JS, Hyun L, Chan C, Chung HS, Eivazi A, Yoder SC, Vielmetter J, Carmichael DF, Hayes RJ, Dahiyat BI. Engineered antibody Fc variants with enhanced effector function. Proc Natl Acad Sci U S A 2006, 103:4005-4010. 10.1073/pnas.0508123103, 1389705, 16537476.
82. Costantini DL, Bateman K, McLarty K, Vallis KA, Reilly RM. Trastuzumab-resistant breast cancer cells remain sensitive to the auger electron-emitting radiotherapeutic agent 111In-NLS-trastuzumab and are radiosensitized by methotrexate. J Nucl Med 2008, 49:1498-1505. 10.2967/jnumed.108.051771, 18703606.