Molecular mechanisms of cardiotoxicity induced by ErbB receptor inhibitor cancer therapeutics

International Journal of Molecular Sciences

Volumn 13, Issue 10, 2012, Pages 12268-12286

  Hervent, Anne Sophie ^a   De Keulenaer, Gilles W ^a  

^a UNIVERSITY OF ANTWERP   (Belgium)

Author keywords

Cancer; Cardiotoxicity; ErbB inhibitors; Heart failure

Indexed keywords

ANTHRACYCLINE; CETUXIMAB; DOXORUBICIN; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; ERLOTINIB; GEFITINIB; GEMCITABINE; LAPATINIB; PACLITAXEL; PANITUMUMAB; PERTUZUMAB; TRASTUZUMAB; ANTINEOPLASTIC AGENT; MONOCLONAL ANTIBODY; PROTEIN KINASE INHIBITOR;

ADD ON THERAPY; ADVANCED CANCER; BINDING AFFINITY; BINDING SITE; BREAST CANCER; CANCER THERAPY; CARCINOGENESIS; CARDIOTOXICITY; CENTRAL NERVOUS SYSTEM METASTASIS; COLORECTAL CANCER; DISEASE ASSOCIATION; DOSE RESPONSE; DRUG EFFICACY; DRUG ERUPTION; DRUG MECHANISM; DRUG POTENTIATION; DRUG SAFETY; DRUG TARGETING; DRUG TOLERABILITY; FOOD AND DRUG ADMINISTRATION; GLIOMA; HEAD AND NECK CARCINOMA; HEART FAILURE; HEART LEFT VENTRICLE EJECTION FRACTION; HEART MUSCLE CELL; HUMAN; INTERSTITIAL PNEUMONIA; LUNG CANCER; LUNG NON SMALL CELL CANCER; METASTASIS; MOLECULAR DYNAMICS; MOLECULAR PATHOLOGY; NONHUMAN; OVARY CANCER; PANCREAS CANCER; PROSTATE CANCER; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SIDE EFFECT; SIGNAL TRANSDUCTION; SQUAMOUS CELL CARCINOMA; ANTAGONISTS AND INHIBITORS; METABOLISM; NEOPLASMS;

ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; HEART FAILURE; HUMANS; NEOPLASMS; PROTEIN KINASE INHIBITORS; RECEPTOR, ERBB-2; SIGNAL TRANSDUCTION;

EID: 84867819154     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms131012268     Document Type: Review

References (103)

1. Stupp, R.; Hegi, M.E.; van den Bent, M.J.; Mason, W.P.; Weller, M.; Mirimanoff, R.O.; Cairncross, J.G. Changing paradigms-An update on the multidisciplinary management of malignant glioma. Oncologist 2006, 11, 165-180.
2. Slamon, D.J.; Leyland-Jones, B.; Shak, S.; Fuchs, H.; Paton, V.; Bajamonde, A.; Fleming, T.; Eiermann, W.; Wolter, J.; Pegram, M. et al. Use of chemotherapy plus a monoclonal antibody against her2 for metastatic breast cancer that overexpresses her2. N. Engl. J. Med. 2001, 344, 783-792.
3. Yap, T.A.; Carden, C.P.; Kaye, S.B. Beyond chemotherapy: Targeted therapies in ovarian cancer. Nat. Rev. Cancer 2009, 9, 167-181.
4. Agus, D.B.; Sweeney, C.J.; Morris, M.J.; Mendelson, D.S.; McNeel, D.G.; Ahmann, F.R.; Wang, J.; Derynck, M.K.; Ng, K.; Lyons, B. et al. Efficacy and safety of single-agent pertuzumab (rhumab 2c4), a human epidermal growth factor receptor dimerization inhibitor, in castration-resistant prostate cancer after progression from taxane-based therapy. J. Clin. Oncol. 2007, 25, 675-681.
5. Starling, N.; Neoptolemos, J.; Cunningham, D. Role of erlotinib in the management of pancreatic cancer. Ther. Clin. Risk Manag. 2006, 2, 435-445.
6. Chung, K.Y.; Shia, J.; Kemeny, N.E.; Shah, M.; Schwartz, G.K.; Tse, A.; Hamilton, A.; Pan, D.; Schrag, D.; Schwartz, L. et al. Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J. Clin. Oncol. 2005, 23, 1803-1810.
7. Bonner, J.A.; Harari, P.M.; Giralt, J.; Azarnia, N.; Shin, D.M.; Cohen, R.B.; Jones, C.U.; Sur, R.; Raben, D.; Jassem, J. et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N. Eng. J. Med. 2006, 354, 567-578.
8. Holbro, T.; Hynes, N.E. Erbb receptors: Directing key signaling networks throughout life. Annu. Rev. Pharmacol. Toxicol. 2004, 44, 195-217.
9. Falls, D.L. Neuregulins: Functions, forms, and signaling strategies. Exp. Cell Res. 2003, 284, 14-30.
10. Burden, S.; Yarden, Y. Neuregulins and their receptors: A versatile signaling module in organogenesis and oncogenesis. Neuron 1997, 18, 847-855.
11. Marmor, M.D.; Skaria, K.B.; Yarden, Y. Signal transduction and oncogenesis by erbb/her receptors. Int. J. Rad. Oncol. Biol. Phys. 2004, 58, 903-913.
12. Keefe, D.L. Trastuzumab-associated cardiotoxicity. Cancer 2002, 95, 1592-1600.
13. Force, T.; Krause, D.S.; van Etten, R.A. Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition. Nat. Rev. Cancer 2007, 7, 332-344.
14. Stevenson, L.W.; Perloff, J.K. The limited reliability of physical signs for estimating hemodynamics in chronic heart failure. J. Am. Med. Assoc. 1989, 261, 884-888.
15. Riese, D.J.; Stern, D.F. Specificity within the egf family/erbb receptor family signaling network. BioEssays 1998, 20, 41-48.
16. Yarden, Y.; Sliwkowski, M.X. Untangling the erbb signalling network. Nat. Rev. 2001, 2, 127-137.
17. Yarden, Y. The egfr family and its ligands in human cancer: Signalling mechanisms and therapeutic opportunities. Eur. J. Cancer 2001, 37 (Suppl. 4), S3-S8.
18. Earp, H.S.; Calvo, B.F.; Sartor, C.I. The egf receptor family-Multiple roles in proliferation, differentiation, and neoplasia with an emphasis on her4. Trans. Am. Clin. Climatol. Assoc. 2003, 114, 315-333; discussion 333-314.
19. Schlessinger, J. Common and distinct elements in cellular signaling via egf and fgf receptors. Science 2004, 306, 1506-1507.
20. Lee, K.F.; Simon, H.; Chen, H.; Bates, B.; Hung, M.C.; Hauser, C. Requirement for neuregulin receptor erbb2 in neural and cardiac development. Nature 1995, 378, 394-398.
21. Gassmann, M.; Casagranda, F.; Orioli, D.; Simon, H.; Lai, C.; Klein, R.; Lemke, G. Aberrant neural and cardiac development in mice lacking the erbb4 neuregulin receptor. Nature 1995, 378, 390-394.
22. Meyer, D.; Birchmeier, C. Multiple essential functions of neuregulin in development. Nature 1995, 378, 386-390.
23. Erickson, S.L.; O'Shea, K.S.; Ghaboosi, N.; Loverro, L.; Frantz, G.; Bauer, M.; Lu, L.H.; Moore, M.W. Erbb3 is required for normal cerebellar and cardiac development: A comparison with erbb2-and heregulin-deficient mice. Development 1997, 124, 4999-5011.
24. Miettinen, P.J.; Berger, J.E.; Meneses, J.; Phung, Y.; Pedersen, R.A.; Werb, Z.; Derynck, R. Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor. Nature 1995, 376, 337-341.
25. Sibilia, M.; Wagner, E.F. Strain-dependent epithelial defects in mice lacking the egf receptor. Science 1995, 269, 234-238.
26. Zhao, Y.Y.; Sawyer, D.R.; Baliga, R.R.; Opel, D.J.; Han, X.; Marchionni, M.A.; Kelly, R.A. Neuregulins promote survival and growth of cardiac myocytes. Persistence of erbb2 and erbb4 expression in neonatal and adult ventricular myocytes. J. Biol. Chem. 1998, 273, 10261-10269.
27. Salomon, D.S.; Brandt, R.; Ciardiello, F.; Normanno, N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit. Rev. Oncol. Hematol. 1995, 19, 183-232.
28. Gorgoulis, V.; Aninos, D.; Mikou, P.; Kanavaros, P.; Karameris, A.; Joardanoglou, J.; Rasidakis, A.; Veslemes, M.; Ozanne, B.; Spandidos, D.A. Expression of egf, tgf-alpha and egfr in squamous cell lung carcinomas. Anticancer Res. 1992, 12, 1183-1187.
29. Irish, J.C.; Bernstein, A. Oncogenes in head and neck cancer. Laryngoscope 1993, 103, 42-52.
30. Ekstrand, A.J.; Sugawa, N.; James, C.D.; Collins, V.P. Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N- and/or C-terminal tails. Proc. Natl. Acad. Sci. USA 1992, 89, 4309-4313.
31. Moscatello, D.K.; Holgado-Madruga, M.; Godwin, A.K.; Ramirez, G.; Gunn, G.; Zoltick, P.W.; Biegel, J.A.; Hayes, R.L.; Wong, A.J. Frequent expression of a mutant epidermal growth factor receptor in multiple human tumors. Cancer Res. 1995, 55, 5536-5539.
32. Benz, C.C.; Scott, G.K.; Sarup, J.C.; Johnson, R.M.; Tripathy, D.; Coronado, E.; Shepard, H.M.; Osborne, C.K. Estrogen-dependent, tamoxifen-resistant tumorigenic growth of mcf-7 cells transfected with her2/neu. Breast Cancer Res. Treat. 1992, 24, 85-95.
33. Yang, H.; Zhao, R.; Yang, H.Y.; Lee, M.H. Constitutively active foxo4 inhibits akt activity, regulates p27 kip1 stability, and suppresses her2-mediated tumorigenicity. Oncogene 2005, 24, 1924-1935.
34. Borg, A.; Baldetorp, B.; Ferno, M.; Killander, D.; Olsson, H.; Sigurdsson, H. Erbb2 amplification in breast cancer with a high rate of proliferation. Oncogene 1991, 6, 137-143.
35. Hynes, N.E.; Stern, D.F. The biology of erbb-2/neu/her-2 and its role in cancer. Biochim. Biophys. Acta 1994, 30, 2-3.
36. Stephens, P.; Hunter, C.; Bignell, G.; Edkins, S.; Davies, H.; Teague, J.; Stevens, C.; O'Meara, S.; Smith, R.; Parker, A. et al. Lung cancer: Intragenic erbb2 kinase mutations in tumours. Nature 2004, 431, 525-526.
37. Holbro, T.; Beerli, R.R.; Maurer, F.; Koziczak, M.; Barbas, C.F., III; Hynes, N.E. The erbb2/erbb3 heterodimer functions as an oncogenic unit: Erbb2 requires erbb3 to drive breast tumor cell proliferation. Proc. Natl. Acad. Sci. USA 2003, 100, 8933-8938.
38. Kew, T.Y.; Bell, J.A.; Pinder, S.E.; Denley, H.; Srinivasan, R.; Gullick, W.J.; Nicholson, R.I.; Blamey, R.W.; Ellis, I.O. C-erbb-4 protein expression in human breast cancer. Br. J. Cancer 2000, 82, 1163-1170.
39. Gilbertson, R.J.; Perry, R.H.; Kelly, P.J.; Pearson, A.D.; Lunec, J. Prognostic significance of her2 and her4 coexpression in childhood medulloblastoma. Cancer Res. 1997, 57, 3272-3280.
40. Iannello, A.; Ahmad, A. Role of antibody-dependent cell-mediated cytotoxicity in the efficacy of therapeutic anti-cancer monoclonal antibodies. Cancer Metastasis Rev. 2005, 24, 487-499.
41. Imai, K.; Takaoka, A. Comparing antibody and small-molecule therapies for cancer. Nat. Rev. Cancer 2006, 6, 714-727.
42. Carter, P.J. Potent antibody therapeutics by design. Nat. Rev. Immunol. 2006, 6, 343-357.
43. Dancey, J.; Sausville, E.A. Issues and progress with protein kinase inhibitors for cancer treatment. Nat. Rev. Drug Discov. 2003, 2, 296-313.
44. Huang, S.; Armstrong, E.A.; Benavente, S.; Chinnaiyan, P.; Harari, P.M. Dual-agent molecular targeting of the epidermal growth factor receptor (egfr): Combining anti-egfr antibody with tyrosine kinase inhibitor. Cancer Res. 2004, 64, 5355-5362.
45. Maitland, M.L.; Ratain, M.J. Terminal ballistics of kinase inhibitors: There are no magic bullets. Ann. Intern. Med. 2006, 145, 702-703.
46. Cheng, H.; Force, T. Why do kinase inhibitors cause cardiotoxicity and what can be done about it? Prog. Cardiovas. Dis. 2010, 53, 114-120.
47. Baselga, J. The egfr as a target for anticancer therapy-Focus on cetuximab. Eur. J. Cancer 2001, 37, S16-S22.
48. Goldberg, R.M. Cetuximab. Nat. Rev. Drug Discov. 2005, 1, S10-S11.
49. Li, S.; Schmitz, K.R.; Jeffrey, P.D.; Wiltzius, J.J.; Kussie, P.; Ferguson, K.M. Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. Cancer Cell 2005, 7, 301-311.
50. Herbst, R.S.; Fukuoka, M.; Baselga, J. Gefitinib [mdash] a novel targeted approach to treating cancer. Nat. Rev. Cancer 2004, 4, 979-987.
51. Minna, J.D.; Dowell, J. Erlotinib hydrochloride. Nat. Rev. Drug Discov. 2005, 5, S14-S15.
52. Jeon, E.K.; Won, H.S.; Ko, Y.H.; Lee, I.S.; Hong, T.H.; You, Y.K.; Lee, M.A. Comparison of the efficacy and the toxicity between gemcitabine with capecitabine (gc) and gemcitabine with erlotinib (ge) in unresectable pancreatic cancer. J. Cancer Res. Clin. Oncol. 2012, 138, 1625-1630.
53. Xia, W.; Gerard, C.M.; Liu, L.; Baudson, N.M.; Ory, T.L.; Spector, N.L. Combining lapatinib (gw572016), a small molecule inhibitor of erbb1 and erbb2 tyrosine kinases, with therapeutic anti-erbb2 antibodies enhances apoptosis of erbb2-overexpressing breast cancer cells. Oncogene 2005, 24, 6213-6221.
54. Silvano, G.; Lazzari, G.; Lovecchio, M.; Palazzo, C. Acute and fatal diarrhoea after erlotinib plus abdominal palliative hypofractionated radiotherapy in a metastatic non-small cell lung cancer patient: A case report. Lung Cancer 2008, 61, 270-273.
55. Inoue, A.; Saijo, Y.; Maemondo, M.; Gomi, K.; Tokue, Y.; Kimura, Y.; Ebina, M.; Kikuchi, T.; Moriya, T.; Nukiwa, T. Severe acute interstitial pneumonia and gefitinib. Lancet 2003, 361, 137-139.
56. Chen, M.H.; Kerkela, R.; Force, T. Mechanisms of cardiac dysfunction associated with tyrosine kinase inhibitor cancer therapeutics. Circulation 2008, 118, 84-95.
57. Slamon, D.J.; Clark, G.M.; Wong, S.G.; Levin, W.J.; Ullrich, A.; McGuire, W.L. Human breast cancer: Correlation of relapse and survival with amplification of the her-2/neu oncogene. Science 1987, 235, 177-182.
58. Romond, E.H.; Perez, E.A.; Bryant, J.; Suman, V.J.; Geyer, C.E.; Davidson, N.E.; Tan-Chiu, E.; Martino, S.; Paik, S.; Kaufman, P.A. et al. Trastuzumab plus adjuvant chemotherapy for operable her2-positive breast cancer. N. Eng. J. Med. 2005, 353, 1673-1684.
59. Dahabreh, I.J.; Linardou, H.; Siannis, F.; Fountzilas, G.; Murray, S. Trastuzumab in the adjuvant treatment of early-stage breast cancer: A systematic review and meta-analysis of randomized controlled trials. Oncologist 2008, 13, 620-630.
60. Joensuu, H.; Kellokumpu-Lehtinen, P.L.; Bono, P.; Alanko, T.; Kataja, V.; Asola, R.; Utriainen, T.; Kokko, R.; Hemminki, A.; Tarkkanen, M. et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N. Engl. J. Med. 2006, 354, 809-820.
61. Hudis, C.A. Trastuzumab-Mechanism of action and use in clinical practice. N. Engl. J. Med. 2007, 357, 39-51.
62. Golay, J.; Introna, M. Mechanism of action of therapeutic monoclonal antibodies: Promises and pitfalls of in vitro and in vivo assays. Arch. Biochem. Biophys. 2012, 526, 146-153.
63. Garrett, T.P.J.; McKern, N.M.; Lou, M.; Elleman, T.C.; Adams, T.E.; Lovrecz, G.O.; Kofler, M.; Jorissen, R.N.; Nice, E.C.; Burgess, A.W. et al. The crystal structure of a truncated erbb2 ectodomain reveals an active conformation, poised to interact with other erbb receptors. Mol. Cell 2003, 11, 495-505.
64. Molina, M.A.; 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.
65. Christianson, T.A.; Doherty, J.K.; Lin, Y.J.; Ramsey, E.E.; Holmes, R.; Keenan, E.J.; Clinton, G.M. Nh2-terminally truncated her-2/neu protein: Relationship with shedding of the extracellular domain and with prognostic factors in breast cancer. Cancer Res. 1998, 58, 5123-5129.
66. Cooley, S.; Burns, L.J.; Repka, T.; Miller, J.S. Natural killer cell cytotoxicity of breast cancer targets is enhanced by two distinct mechanisms of antibody-dependent cellular cytotoxicity against lfa-3 and her2/neu. Exp. Hematol. 1999, 27, 1533-1541.
67. Clynes, R.A.; Towers, T.L.; Presta, L.G.; Ravetch, J.V. Inhibitory fc receptors modulate in vivo cytotoxicity against tumor targets. Nat. Med. 2000, 6, 443-446.
68. Cameron, D.A.; Stein, S. Drug insight: Intracellular inhibitors of her2[mdash]clinical development of lapatinib in breast cancer. Nat. Clin. Prac. Oncol. 2008, 5, 512-520.
69. Valachis, A.; Nearchou, A.; Lind, P.; Mauri, D. Lapatinib, trastuzumab or the combination added to preoperative chemotherapy for breast cancer: A meta-analysis of randomized evidence. Breast Cancer Res. Treat. 2012, 135, 655-662.
70. Baselga, J.; Bradbury, I.; Eidtmann, H.; Di Cosimo, S.; de Azambuja, E.; Aura, C.; Gomez, H.; Dinh, P.; Fauria, K.; van Dooren, V. et al. Lapatinib with trastuzumab for her2-positive early breast cancer (neoaltto): A randomised, open-label, multicentre, phase 3 trial. Lancet 2012, 379, 633-640.
71. Rusnak, D.W.; Lackey, K.; Affleck, K.; Wood, E.R.; Alligood, K.J.; Rhodes, N.; Keith, B.R.; Murray, D.M.; Knight, W.B.; Mullin, R.J. et al. The effects of the novel, reversible epidermal growth factor receptor/erbb-2 tyrosine kinase inhibitor, gw2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo. Mol. Cancer Ther. 2001, 1, 85-94.
72. Taskar, K.S.; Rudraraju, V.; Mittapalli, R.K.; Samala, R.; Thorsheim, H.R.; Lockman, J.; Gril, B.; Hua, E.; Palmieri, D.; Polli, J.W. et al. Lapatinib distribution in her2 overexpressing experimental brain metastases of breast cancer. Pharm. Res. 2012, 29, 770-781.
73. Lim, E.; Lin, N.U. New insights and emerging therapies for breast cancer brain metastases. Oncology 2012, 26, 652-659, 663.
74. Agus, D.B.; Akita, R.W.; Fox, W.D.; Lewis, G.D.; Higgins, B.; Pisacane, P.I.; Lofgren, J.A.; Tindell, C.; Evans, D.P.; Maiese, K. et al. Targeting ligand-activated erbb2 signaling inhibits breast and prostate tumor growth. Cancer Cell 2002, 2, 127-137.
75. Gordon, M.S.; Matei, D.; Aghajanian, C.; Matulonis, U.A.; Brewer, M.; Fleming, G.F.; Hainsworth, J.D.; Garcia, A.A.; Pegram, M.D.; Schilder, R.J. et al. Clinical activity of pertuzumab (rhumab 2c4), a her dimerization inhibitor, in advanced ovarian cancer: Potential predictive relationship with tumor her2 activation status. J. Clin. Oncol. 2006, 24, 4324-4332.
76. Gianni, L.; Llado, A.; Bianchi, G.; Cortes, J.; Kellokumpu-Lehtinen, P.L.; Cameron, D.A.; Miles, D.; Salvagni, S.; Wardley, A.; Goeminne, J.C. et al. Open-label, phase ii, multicenter, randomized study of the efficacy and safety of two dose levels of pertuzumab, a human epidermal growth factor receptor 2 dimerization inhibitor, in patients with human epidermal growth factor receptor 2-negative metastatic breast cancer. J. Clin. Oncol. 2010, 28, 1131-1137.
77. De Bono, J.S.; Bellmunt, J.; Attard, G.; Droz, J.P.; Miller, K.; Flechon, A.; Sternberg, C.; Parker, C.; Zugmaier, G.; Hersberger-Gimenez, V. et al. Open-label phase ii study evaluating the efficacy and safety of two doses of pertuzumab in castrate chemotherapy-naive patients with hormone-refractory prostate cancer. J. Clin. Oncol. 2007, 25, 257-262.
78. Herbst, R.S.; Davies, A.M.; Natale, R.B.; Dang, T.P.; Schiller, J.H.; Garland, L.L.; Miller, V.A.; Mendelson, D.; van den Abbeele, A.D.; Melenevsky, Y. et al. Efficacy and safety of single-agent pertuzumab, a human epidermal receptor dimerization inhibitor, in patients with non small cell lung cancer. Clin. Cancer Res. 2007, 13, 6175-6181.
79. Cho, H.S.; Mason, K.; Ramyar, K.X.; Stanley, A.M.; Gabelli, S.B.; Denney, D.W., Jr.; Leahy, D.J. Structure of the extracellular region of her2 alone and in complex with the herceptin fab. Nature 2003, 421, 756-760.
80. Franklin, M.C.; Carey, K.D.; Vajdos, F.F.; Leahy, D.J.; de Vos, A.M.; Sliwkowski, M.X. Insights into erbb signaling from the structure of the erbb2-pertuzumab complex. Cancer Cell 2004, 5, 317-328.
81. Gianni, L.; Pienkowski, T.; Im, Y.H.; Roman, L.; Tseng, L.M.; Liu, M.C.; Lluch, A.; Staroslawska, E.; de la Haba-Rodriguez, J.; Im, S.A. et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early her2-positive breast cancer (neosphere): A randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012, 13, 25-32.
82. Baselga, J.; Cortes, J.; Kim, S.B.; Im, S.A.; Hegg, R.; Im, Y.H.; Roman, L.; Pedrini, J.L.; Pienkowski, T.; Knott, A. et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N. Engl. J. Med. 2012, 366, 109-119.
83. Lemmens, K.; Segers, V.F.; Demolder, M.; de Keulenaer, G.W. Role of neuregulin-1/erbb2 signaling in endothelium-cardiomyocyte cross-talk. J. Biol. Chem. 2006, 281, 19469-19477.
84. Bersell, K.; Arab, S.; Haring, B.; Kühn, B. Neuregulin1/erbb4 signaling induces cardiomyocyte proliferation and repair of heart injury. Cell 2009, 138, 257-270.
85. Kuramochi, Y.; Guo, X.; Sawyer, D.B. Neuregulin activates erbb2-dependent src/fak signaling and cytoskeletal remodeling in isolated adult rat cardiac myocytes. J. Mol. Cell. Cardiol. 2006, 41, 228-235.
86. Russell, K.S.; Stern, D.F.; Polverini, P.J.; Bender, J.R. Neuregulin activation of erbb receptors in vascular endothelium leads to angiogenesis. Am. J. Physiol. 1999, 277, H2205-H2211.
87. Lemmens, K.; Fransen, P.; Sys, S.U.; Brutsaert, D.L.; de Keulenaer, G.W. Neuregulin-1 induces a negative inotropic effect in cardiac muscle: Role of nitric oxide synthase. Circulation 2004, 109, 324-326.
88. De Keulenaer, G.W.; Doggen, K.; Lemmens, K. The vulnerability of the heart as a pluricellular paracrine organ: Lessons from unexpected triggers of heart failure in targeted erbb2 anticancer therapy. Circ. Res. 2010, 106, 35-46.
89. Seidman, A.; Hudis, C.; Pierri, M.K.; Shak, S.; Paton, V.; Ashby, M.; Murphy, M.; Stewart, S.J.; Keefe, D. Cardiac dysfunction in the trastuzumab clinical trials experience. J. Clin. Oncol. 2002, 20, 1215-1221.
90. Ewer, M.S.; Vooletich, M.T.; Durand, J.B.; Woods, M.L.; Davis, J.R.; Valero, V.; Lenihan, D.J. Reversibility of trastuzumab-related cardiotoxicity: New insights based on clinical course and response to medical treatment. J. Clin. Oncol. 2005, 23, 7820-7826.
91. Sawyer, D.B.; Peng, X.; Chen, B.; Pentassuglia, L.; Lim, C.C. Mechanisms of anthracycline cardiac injury: Can we identify strategies for cardioprotection? Prog. Cardiovasc. Dis. 2010, 53, 105-113.
92. Octavia, Y.; Tocchetti, C.G.; Gabrielson, K.L.; Janssens, S.; Crijns, H.J.; Moens, A.L. Doxorubicin-induced cardiomyopathy: From molecular mechanisms to therapeutic strategies. J. Mol. Cell. Cardiol. 2012, 52, 1213-1225.
93. Gianni, L.; Herman, E.H.; Lipshultz, S.E.; Minotti, G.; Sarvazyan, N.; Sawyer, D.B. Anthracycline cardiotoxicity: From bench to bedside. J. Clin. Oncol. 2008, 26, 3777-3784.
94. Burris, H.A., III; Hurwitz, H.I.; Dees, E.C.; Dowlati, A.; Blackwell, K.L.; O'Neil, B.; Marcom, P.K.; Ellis, M.J.; Overmoyer, B.; Jones, S.F. et al. Phase i safety, pharmacokinetics, and clinical activity study of lapatinib (gw572016), a reversible dual inhibitor of epidermal growth factor receptor tyrosine kinases, in heavily pretreated patients with metastatic carcinomas. J. Clin. Oncol. 2005, 23, 5305-5313.
95. Geyer, C.E.; Forster, J.; Lindquist, D.; Chan, S.; Romieu, C.G.; Pienkowski, T.; Jagiello-Gruszfeld, A.; Crown, J.; Chan, A.; Kaufman, B. et al. Lapatinib plus capecitabine for her2-positive advanced breast cancer. N. Engl. J. Med. 2006, 355, 2733-2743.
96. De Azambuja, E.; Bedard, P.; Suter, T.; Piccart-Gebhart, M. Cardiac toxicity with anti-her-2 therapies-what have we learned so far? Target. Oncol. 2009, 4, 77-88.
97. Sliwkowski, M.X.; Lofgren, J.A.; Lewis, G.D.; Hotaling, T.E.; Fendly, B.M.; Fox, J.A. Nonclinical studies addressing the mechanism of action of trastuzumab (herceptin). Semin. Oncol. 1999, 26, 60-70.
98. Lenihan, D.; Suter, T.; Brammer, M.; Neate, C.; Ross, G.; Baselga, J. Pooled analysis of cardiac safety in patients with cancer treated with pertuzumab. Ann. Oncol. 2012, 23, 791-800.
99. Shell, S.A.; Lyass, L.; Trusk, P.B.; Pry, K.J.; Wappel, R.L.; Bacus, S.S. Activation of ampk is necessary for killing cancer cells and sparing cardiac cells. Cell Cycle 2008, 7, 1769-1775.
100. Spector, N.L.; Yarden, Y.; Smith, B.; Lyass, L.; Trusk, P.; Pry, K.; Hill, J.E.; Xia, W.; Seger, R.; Bacus, S.S. Activation of amp-activated protein kinase by human egf receptor 2/egf receptor tyrosine kinase inhibitor protects cardiac cells. Proc. Natl. Acad. Sci. USA 2007, 104, 10607-10612.
101. Jathal, M.K.; Chen, L.; Mudryj, M.; Ghosh, P.M. Targeting erbb3: The new rtk(id) on the prostate cancer block. Immun. Endocr. Metab. Agents Med. Chem. 2011, 11, 131-149.
102. McDonagh, C.F.; Huhalov, A.; Harms, B.D.; Adams, S.; Paragas, V.; Oyama, S.; Zhang, B.; Luus, L.; Overland, R.; Nguyen, S. et al. Antitumor activity of a novel bispecific antibody that targets the erbb2/erbb3 oncogenic unit and inhibits heregulin-induced activation of erbb3. Mol. Cancer Ther. 2012, doi:10.1158/1535-7163.MCT-11-0820.
103. Langdon, S.P.; Faratian, D.; Nagumo, Y.; Mullen, P.; Harrison, D.J. Pertuzumab for the treatment of ovarian cancer. Exp. Opin. Biol. Ther. 2010, 10, 1113-1120.