Pharmacological strategies to overcome HER2 cross-talk and trastuzumab resistance

Current Medicinal Chemistry

Volumn 19, Issue 7, 2012, Pages 1065-1075

  Nahta, R ^a,b  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b EMORY UNIVERSITY   (United States)

Author keywords

Breast cancer; Cross talk; erbB2; FAK; Her2; Herceptin; IGF IR; Lapatinib; Pertuzumab; Resistance; TGF beta; Trastuzumab; VEGF

Indexed keywords

2 MORPHOLINO 8 PHENYLCHROMONE; 2 [5 CHLORO 2 (2 METHOXY 4 MORPHOLINOANILINO) 4 PYRIMIDINYLAMINO] N METHYLBENZAMIDE; 4 AMINO 7 TERT BUTYL 5 (4 CHLOROPHENYL)PYRAZOLO[3,4 D]PYRIMIDINE; 4 [4 (1,3 BENZODIOXOL 5 YL) 5 (2 PYRIDINYL) 1H IMIDAZOL 2 YL]BENZAMIDE; AG 538; ANTINEOPLASTIC AGENT; BMS 536924; DALOTUZUMAB; DASATINIB; DOCETAXEL; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EVEROLIMUS; FOCAL ADHESION KINASE; LAPATINIB; MAMMALIAN TARGET OF RAPAMYCIN; NVP AEW 541; PERTUZUMAB; PHOSPHATIDYLINOSITOL 3 KINASE; PLACEBO; RAPAMYCIN; RIDAFOROLIMUS; SARACATINIB; TEMSIROLIMUS; TRANSFORMING GROWTH FACTOR BETA; TRASTUZUMAB; TRICIRIBINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULOTROPIN; VASCULOTROPIN INHIBITOR; [1 (4 OXO 8 PHENYL 4H 1 BENZOPYRAN 2 YL)MORPHOLINIO]METHOXYSUCCINYLARGINYLGLYCYLASPARTYLSERINE ACETATE;

ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; ANTINEOPLASTIC ACTIVITY; BREAST CANCER; BREAST CARCINOGENESIS; CANCER GROWTH; CANCER IMMUNOTHERAPY; CANCER RESISTANCE; CANCER SURVIVAL; DIMERIZATION; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENTIATION; GENE OVEREXPRESSION; HUMAN; NONHUMAN; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROGRESSION FREE SURVIVAL; REVIEW; SIGNAL TRANSDUCTION; TREATMENT RESPONSE; UNSPECIFIED SIDE EFFECT;

EID: 84858189073     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/092986712799320691     Document Type: Review

References (99)

1. 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(4785), 177-182.
2. Baselga, J.; Tripathy, D.; Mendelsohn, J.; Baughman, S.; Benz, C.C.; Dantis, L.; Sklarin, N.T.; Seidman, A.D.; Hudis, C.A.; Moore, J.; Rosen, P.P.; Twaddell, T.; Henderson, I.C.; Norton, L. Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J Clin Oncol, 1996, 14(3), 737-744.
3. Cobleigh, M.A.; Vogel, C.L.; Tripathy, D.; Robert, N.J.; Scholl, S.; Fehrenbacher, L.; Wolter, J.M.; Paton, V.; Shak, S.; Lieberman, G.; Slamon, D.J. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol, 1999, 17(9), 2639-2648. (Pubitemid 29415219)
4. Geyer, C.E.; Forster, J.; Lindquist, D.; Chan, S.; Romieu, C.G.; Pienkowski, T.; Jagiello-Gruszfeld, A.; Crown, J.; Chan, A.; Kaufman, B.; Skarlos, D.; Campone, M.; Davidson, N.; Berger, M.; Oliva, C.; Rubin, S.D.; Stein, S.; Cameron, D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med, 2006, 355(26), 2733-2743. (Pubitemid 46021510)
5. Slamon, D.J.; 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(11), 783-792. (Pubitemid 32222155)
6. Esteva, F.J.; Valero, V.; Booser, D.; Guerra, L.T.; Murray, J.L.; Pusztai, L.; Cristofanilli, M.; Arun, B.; Esmaeli, B.; Fritsche, H.A.; Sneige, N.; Smith, T.L.; Hortobagyi, G.N. Phase II study of weekly docetaxel and trastuzumab for patients with HER-2-overexpressing metastatic breast cancer. J Clin Oncol, 2002, 20(7), 1800-1808. (Pubitemid 34273269)
7. Seidman, A.D.; Fornier, M.N.; Esteva, F.J.; Tan, L.; Kaptain, S.; Bach, A.; Panageas, K.S.; Arroyo, C.; Valero, V.; Currie, V.; Gilewski, T.; Theodoulou, M.; Moynahan, M.E.; Moasser, M.; Sklarin, N.; Dickler, M.; D'Andrea, G.; Cristofanilli, M.; Rivera, E.; Hortobagyi, G.N.; Norton, L.; Hudis, C.A. Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification. J Clin Oncol, 2001, 19(10), 2587-2595. (Pubitemid 32441364)
8. Bender, L.M.; Nahta, R. Her2 cross talk and therapeutic resistance in breast cancer. Front Biosci, 2008, 13, 3906-3912. (Pubitemid 351594668)
9. Graus-Porta, D.; Beerli, R.R.; Daly, J.M.; Hynes, N.E. ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. EMBO J, 1997, 16(7), 1647-1655. (Pubitemid 27151960)
10. Motoyama, A.B.; Hynes, N.E.; Lane, H.A. The efficacy of ErbB receptor-targeted anticancer therapeutics is influenced by the availability of epidermal growth factor-related peptides. Cancer Res, 2002, 62(11), 3151-3158. (Pubitemid 34602408)
11. Moulder, S.L.; Yakes, F.M.; Muthuswamy, S.K.; Bianco, R.; Simpson, J.F.; Arteaga, C.L. Epidermal growth factor receptor (HER1) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo. Cancer Res, 2001, 61(24), 8887-8895. (Pubitemid 34013905)
12. Ritter, C.A.; Perez-Torres, M.; Rinehart, C.; Guix, M.; Dugger, T.; Engelman, J.A.; Arteaga, C.L. Human breast cancer cells selected for resistance to trastuzumab in vivo overexpress epidermal growth factor receptor and ErbB ligands and remain dependent on the ErbB receptor network. Clin Cancer Res, 2007, 13(16), 4909-4919. (Pubitemid 47294799)
13. Lee-Hoeflich, S.T.; Crocker, L.; Yao, E.; Pham, T.; Munroe, X.; Hoeflich, K.P.; Sliwkowski, M.X.; Stern, H.M. A central role for HER3 in HER2- amplified breast cancer: implications for targeted therapy. Cancer Res, 2008, 68(14), 5878-5887.
14. Alimandi, M.; Romano, A.; Curia, M.C.; Muraro, R.; Fedi, P.; Aaronson, S.A.; Di Fiore, P.P.; Kraus, M.H. Cooperative signaling of ErbB3 and ErbB2 in neoplastic transformation and human mammary carcinomas. Oncogene, 1995, 10(9), 1813-1821.
15. Holbro, T.; Beerli, R.R.; Maurer, F.; Koziczak, M.; Barbas, C.F., 3rd; 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 U S A, 2003, 100(15), 8933-8938. (Pubitemid 36899201)
16. Hellyer, N.J.; Cheng, K.; Koland, J.G. ErbB3 (HER3) interaction with the p85 regulatory subunit of phosphoinositide 3-kinase. Biochem J, 1998, 333 (Pt 3), 757-763. (Pubitemid 28398546)
17. Siegel, P.M.; Ryan, E.D.; Cardiff, R.D.; Muller, W.J. Elevated expression of activated forms of Neu/ErbB-2 and ErbB-3 are involved in the induction of mammary tumors in transgenic mice: implications for human breast cancer. EMBO J, 1999, 18(8), 2149-2164. (Pubitemid 29179172)
18. van der Horst, E.H.; Murgia, M.; Treder, M.; Ullrich, A. Anti-HER-3 MAbs inhibit HER-3-mediated signaling in breast cancer cell lines resistant to anti- HER-2 antibodies. Int J Cancer, 2005, 115(4), 519-527. (Pubitemid 40656708)
19. Ghosh, R.; Narasanna, A.; Wang, S.E.; Liu, S.; Chakrabarty, A.; Balko, J.M.; Gonzalez-Angulo, A.M.; Mills, G.B.; Penuel, E.; Winslow, J.; Sperinde, J.; Dua, R.; Pidaparthi, S.; Mukherjee, A.; Leitzel, K.; Kostler, W.J.; Lipton, A.; Bates, M.; Arteaga, C.L. Trastuzumab has preferential activity against breast cancers driven by HER2 homodimers. Cancer Res, 2011, 71(5), 1871-1882.
20. Scheuer, W.; Friess, T.; Burtscher, H.; Bossenmaier, B.; Endl, J.; Hasmann, M. Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Res, 2009, 69(24), 9330-9336.
21. Nahta, R.; Hung, M.C.; Esteva, F.J. The HER-2-targeting antibodies trastuzumab and pertuzumab synergistically inhibit the survival of breast cancer cells. Cancer Res, 2004, 64(7), 2343-2346. (Pubitemid 38523885)
22. Xia, W.; Liu, L.H.; Ho, P.; Spector, N.L. Truncated ErbB2 receptor (p95ErbB2) is regulated by heregulin through heterodimer formation with ErbB3 yet remains sensitive to the dual EGFR/ErbB2 kinase inhibitor GW572016. Oncogene, 2004, 23(3), 646-653. (Pubitemid 38241266)
23. Yao, E.; Zhou, W.; Lee-Hoeflich, S.T.; Truong, T.; Haverty, P.M.; Eastham- Anderson, J.; Lewin-Koh, N.; Gunter, B.; Belvin, M.; Murray, L.J.; Friedman, L.S.; Sliwkowski, M.X.; Hoeflich, K.P. 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(12), 4147-4156.
24. Nahta, R.; Yuan, L.X.; Zhang, B.; Kobayashi, R.; Esteva, F.J. Insulin-like growth factor-I receptor/human epidermal growth factor receptor 2 heterodimerization contributes to trastuzumab resistance of breast cancer cells. Cancer Res, 2005, 65(23), 11118-11128. (Pubitemid 41713383)
25. Baselga, J.; Gelmon, K.A.; Verma, S.; Wardley, A.; Conte, P.; Miles, D.; Bianchi, G.; Cortes, J.; McNally, V.A.; Ross, G.A.; Fumoleau, P.; Gianni, L. Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapy. J Clin Oncol, 2010, 28(7), 1138-1144.
26. Baselga, J.; Swain, S.M. CLEOPATRA: a phase III evaluation of pertuzumab and trastuzumab for HER2-positive metastatic breast cancer. Clin Breast Cancer, 2010, 10(6), 489-491.
27. Huang, X.; Gao, L.; Wang, S.; McManaman, J.L.; Thor, A.D.; Yang, X.; Esteva, F.J.; Liu, B. Heterotrimerization of the growth factor receptors erbB2, erbB3, and insulin-like growth factor-i receptor in breast cancer cells resistant to herceptin. Cancer Res, 2010, 70(3), 1204-1214.
28. Nahta, R.; Yuan, L.X.; Du, Y.; Esteva, F.J. Lapatinib induces apoptosis in trastuzumab-resistant breast cancer cells: effects on insulin-like growth factor I signaling. Mol Cancer Ther, 2007, 6(2), 667-674. (Pubitemid 46332467)
29. Law, J.H.; Habibi, G.; Hu, K.; Masoudi, H.; Wang, M.Y.; Stratford, A.L.; Park, E.; Gee, J.M.; Finlay, P.; Jones, H.E.; Nicholson, R.I.; Carboni, J.; Gottardis, M.; Pollak, M.; Dunn, S.E. Phosphorylated insulin-like growth factor-i/insulin receptor is present in all breast cancer subtypes and is related to poor survival. Cancer Res, 2008, 68(24), 10238-10246.
30. Smith, B.L.; Chin, D.; Maltzman, W.; Crosby, K.; Hortobagyi, G.N.; Bacus, S.S. The efficacy of Herceptin therapies is influenced by the expression of other erbB receptors, their ligands and the activation of downstream signalling proteins. Br J Cancer, 2004, 91(6), 1190-1194. (Pubitemid 39336261)
31. Kostler, W.J.; Hudelist, G.; Rabitsch, W.; Czerwenka, K.; Muller, R.; Singer, C.F.; Zielinski, C.C. Insulin-like growth factor-1 receptor (IGF-1R) expression does not predict for resistance to trastuzumab-based treatment inpatients with Her-2/neu overexpressing metastatic breast cancer. J Cancer Res Clin Oncol, 2006, 132(1), 9-18. (Pubitemid 41712801)
32. Tanner, M.; Kapanen, A.I.; Junttila, T.; Raheem, O.; Grenman, S.; Elo, J.; Elenius, K.; Isola, J. Characterization of a novel cell line established from a patient with Herceptin-resistant breast cancer. Mol Cancer Ther, 2004, 3(12), 1585-1592. (Pubitemid 40136714)
33. Oliveras-Ferraros, C.; Vazquez-Martin, A.; Martin-Castillo, B.; Perez- Martinez, M.C.; Cufi, S.; Del Barco, S.; Bernado, L.; Brunet, J.; Lopez- Bonet, E.; Menendez, J.A. Pathway-focused proteomic signatures in HER2- overexpressing breast cancer with a basal-like phenotype: new insights into de novo resistance to trastuzumab (Herceptin). Int J Oncol, 2010, 37(3), 669-678.
34. Harris, L.N.; You, F.; Schnitt, S.J.; Witkiewicz, A.; Lu, X.; Sgroi, D.; Ryan, P.D.; Come, S.E.; Burstein, H.J.; Lesnikoski, B.A.; Kamma, M.; Friedman, P.N.; Gelman, R.; Iglehart, J.D.; Winer, E.P. Predictors of resistance to preoperative trastuzumab and vinorelbine for HER2-positive early breast cancer. Clin Cancer Res, 2007, 13(4), 1198-1207. (Pubitemid 46424061)
35. Garcia-Echeverria, C.; Pearson, M.A.; Marti, A.; Meyer, T.; Mestan, J.; Zimmermann, J.; Gao, J.; Brueggen, J.; Capraro, H.G.; Cozens, R.; Evans, D.B.; Fabbro, D.; Furet, P.; Porta, D.G.; Liebetanz, J.; Martiny-Baron, G.; Ruetz, S.; Hofmann, F. In vivo antitumor activity of NVP-AEW541-A novel, potent, and selective inhibitor of the IGF-IR kinase. Cancer Cell, 2004, 5(3), 231-239. (Pubitemid 38402115)
36. Esparis-Ogando, A.; Ocana, A.; Rodriguez-Barrueco, R.; Ferreira, L.; Borges, J.; Pandiella, A. Synergic antitumoral effect of an IGF-IR inhibitor and trastuzumab on HER2-overexpressing breast cancer cells. Ann Oncol, 2008, 19(11), 1860-1869.
37. Rowe, D.L.; Ozbay, T.; Bender, L.M.; Nahta, R. Nordihydroguaiaretic acid, a cytotoxic insulin-like growth factor-I receptor/HER2 inhibitor in trastuzumab-resistant breast cancer. Mol Cancer Ther, 2008, 7(7), 1900-1908.
38. Klos, K.S.; Wyszomierski, S.L.; Sun, M.; Tan, M.; Zhou, X.; Li, P.; Yang, W.; Yin, G.; Hittelman, W.N.; Yu, D. ErbB2 increases vascular endothelial growth factor protein synthesis via activation of mammalian target of rapamycin/p70S6K leading to increased angiogenesis and spontaneous metastasis of human breast cancer cells. Cancer Res, 2006, 66(4), 2028-2037.
39. Schoppmann, S.F.; Tamandl, D.; Roberts, L.; Jomrich, G.; Schoppmann, A.; Zwrtek, R.; Dubsky, P.; Gnant, M.; Jakesz, R.; Birner, P. HER2/neu expression correlates with vascular endothelial growth factor-C and lymphangiogenesis in lymph node-positive breast cancer. Ann Oncol, 2010, 21(5), 955-960.
40. Yang, W.; Klos, K.; Yang, Y.; Smith, T.L.; Shi, D.; Yu, D. ErbB2 overexpression correlates with increased expression of vascular endothelial growth factors A, C, and D in human breast carcinoma. Cancer, 2002, 94(11), 2855-2861. (Pubitemid 34547683)
41. Tai, W.; Qin, B.; Cheng, K. Inhibition of breast cancer cell growth and invasiveness by dual silencing of HER-2 and VEGF. Molecular pharmaceutics, 2010, 7(2), 543-556.
42. Konecny, G.E.; Meng, Y.G.; Untch, M.; Wang, H.J.; Bauerfeind, I.; Epstein, M.; Stieber, P.; Vernes, J.M.; Gutierrez, J.; Hong, K.; Beryt, M.; Hepp, H.; Slamon, D.J.; Pegram, M.D. Association between HER-2/neu and vascular endothelial growth factor expression predicts clinical outcome in primary breast cancer patients. Clin Cancer Res, 2004, 10(5), 1706-1716. (Pubitemid 38435562)
43. Le, X.F.; Mao, W.; Lu, C.; Thornton, A.; Heymach, J.V.; Sood, A.K.; Bast, R.C., Jr. Specific blockade of VEGF and HER2 pathways results in greater growth inhibition of breast cancer xenografts that overexpress HER2. Cell Cycle, 2008, 7(23), 3747-3758.
44. Foy, K.C.; Liu, Z.; Phillips, G.; Miller, M.; Kaumaya, P.T. Combination treatment with HER-2 and VEGF peptide mimics induces potent anti-tumor and anti-angiogenic responses in vitro and in vivo. J Biol Chem, 2011, 286(15), 13626-13637.
45. du Manoir, J.M.; Francia, G.; Man, S.; Mossoba, M.; Medin, J.A.; Viloria- Petit, A.; Hicklin, D.J.; Emmenegger, U.; Kerbel, R.S. Strategies for delaying or treating in vivo acquired resistance to trastuzumab in human breast cancer xenografts. Clin Cancer Res, 2006, 12(3 Pt 1), 904-916.
46. Burstein, H.J.; Elias, A.D.; Rugo, H.S.; Cobleigh, M.A.; Wolff, A.C.; Eisenberg, P.D.; Lehman, M.; Adams, B.J.; Bello, C.L.; DePrimo, S.E.; Baum, C.M.; Miller, K.D. Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol, 2008, 26(11), 1810-1816.
47. Valabrega, G.; Capellero, S.; Cavalloni, G.; Zaccarello, G.; Petrelli, A.; Migliardi, G.; Milani, A.; Peraldo-Neia, C.; Gammaitoni, L.; Sapino, A.; Pecchioni, C.; Moggio, A.; Giordano, S.; Aglietta, M.; Montemurro, F. HER2-positive breast cancer cells resistant to trastuzumab and lapatinib lose reliance upon HER2 and are sensitive to the multitargeted kinase inhibitor sorafenib. Breast Cancer Res Treat, 2011, 130(1), 29-40.
48. Falchook, G.S.W., J. J.; Naing, A.; Hong, D. S.; Moulder, S. L.; Piha-Paul, S. A.; Ng, C. S.; Jackson, E.; Kurzrock, R. In J Clin Oncol, 2010 ASCO Annual Meeting, A phase I study of bevaizumab in combination with sunitinib, sorafenib, and erlotinib plus cetuximab, and trastuzumab plus lapatinib: 2010; p 15s.
49. Nakamura, K.; Taguchi, E.; Miura, T.; Yamamoto, A.; Takahashi, K.; Bichat, F.; Guilbaud, N.; Hasegawa, K.; Kubo, K.; Fujiwara, Y.; Suzuki, R.; Shibuya, M.; Isae, T. KRN951, a highly potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, has antitumor activities and affects functional vascular properties. Cancer Res, 2006, 66(18), 9134-9142.
50. Osipo, C.; Patel, P.; Rizzo, P.; Clementz, A.G.; Hao, L.; Golde, T.E.; Miele, L. ErbB-2 inhibition activates Notch-1 and sensitizes breast cancer cells to a gamma-secretase inhibitor. Oncogene, 2008, 27(37), 5019-5032.
51. Pandya, K.; Meeke, K.; Clementz, A.G.; Rogowski, A.; Roberts, J.; Miele, L.; Albain, K.S.; Osipo, C. Targeting both Notch and ErbB-2 signalling pathways is required for prevention of ErbB-2-positive breast tumour recurrence. Br J Cancer, 2011, 105(6), 796-806.
52. Muraoka, R.S.; Koh, Y.; Roebuck, L.R.; Sanders, M.E.; Brantley-Sieders, D.; Gorska, A.E.; Moses, H.L.; Arteaga, C.L. Increased malignancy of Neuinduced mammary tumors overexpressing active transforming growth factor beta1. Mol Cell Biol, 2003, 23(23), 8691-8703. (Pubitemid 37433371)
53. Siegel, P.M.; Shu, W.; Cardiff, R.D.; Muller, W.J.; Massague, J. Transforming growth factor beta signaling impairs Neu-induced mammary tumorigenesis while promoting pulmonary metastasis. Proc Natl Acad Sci U S A, 2003, 100(14), 8430-8435. (Pubitemid 36842562)
54. Seton-Rogers, S.E.; Lu, Y.; Hines, L.M.; Koundinya, M.; LaBaer, J.; Muthuswamy, S.K.; Brugge, J.S. Cooperation of the ErbB2 receptor and transforming growth factor beta in induction of migration and invasion in mammary epithelial cells. Proc Natl Acad Sci U S A, 2004, 101(5), 1257-1262. (Pubitemid 38182676)
55. Bandyopadhyay, A.; Lopez-Casillas, F.; Malik, S.N.; Montiel, J.L.; Mendoza, V.; Yang, J.; Sun, L.Z. Antitumor activity of a recombinant soluble betaglycan in human breast cancer xenograft. Cancer Res, 2002, 62(16), 4690-4695.
56. Wang, S.E. The Functional Crosstalk between HER2 Tyrosine Kinase and TGF-beta Signaling in Breast Cancer Malignancy. J Signal Transduct, 2011, 2011, 804236.
57. Wang, S.E.; Wu, F.Y.; Shin, I.; Qu, S.; Arteaga, C.L. Transforming growth factor {beta} (TGF-{beta})-Smad target gene protein tyrosine phosphatase receptor type kappa is required for TGF-{beta} function. Mol Cell Biol, 2005, 25(11), 4703-4715. (Pubitemid 40705773)
58. Ueda, Y.; Wang, S.; Dumont, N.; Yi, J.Y.; Koh, Y.; Arteaga, C.L. Overexpression of HER2 (erbB2) in human breast epithelial cells unmasks transforming growth factor beta-induced cell motility. J Biol Chem, 2004, 279(23), 24505-24513. (Pubitemid 38725316)
59. Wang, S.E.; Xiang, B.; Guix, M.; Olivares, M.G.; Parker, J.; Chung, C.H.; Pandiella, A.; Arteaga, C.L. Transforming growth factor beta engages TACE and ErbB3 to activate phosphatidylinositol-3 kinase/Akt in ErbB2-overexpressing breast cancer and desensitizes cells to trastuzumab. Mol Cell Biol, 2008, 28(18), 5605-5620.
60. Landis, M.D.; Seachrist, D.D.; Montanez-Wiscovich, M.E.; Danielpour, D.; Keri, R.A. Gene expression profiling of cancer progression reveals intrinsic regulation of transforming growth factor-beta signaling in ErbB2/Neu-induced tumors from transgenic mice. Oncogene, 2005, 24(33), 5173-5190. (Pubitemid 41192434)
61. Basolo, F.; Fiore, L.; Ciardiello, F.; Calvo, S.; Fontanini, G.; Conaldi, P.G.; Toniolo, A. Response of normal and oncogene-transformed human mammary epithelial cells to transforming growth factor beta 1 (TGF-beta 1): lack of growth-inhibitory effect on cells expressing the simian virus 40 large-T antigen. Int J Cancer, 1994, 56(5), 736-742. (Pubitemid 24086779)
62. Dowdy, S.C.; Mariani, A.; Janknecht, R. HER2/Neu- and TAK1-mediated up-regulation of the transforming growth factor beta inhibitor Smad7 via the ETS protein ER81. J Biol Chem, 2003, 278(45), 44377-44384. (Pubitemid 37377186)
63. Arnal-Estape, A.; Tarragona, M.; Morales, M.; Guiu, M.; Nadal, C.; Massague, J.; Gomis, R.R. HER2 silences tumor suppression in breast cancer cells by switching expression of C/EBPss isoforms. Cancer Res, 2010, 70(23), 9927-9936.
64. Wilson, C.A.; Cajulis, E.E.; Green, J.L.; Olsen, T.M.; Chung, Y.A.; Damore, M.A.; Dering, J.; Calzone, F.J.; Slamon, D.J. HER-2 overexpression differentially alters transforming growth factor-beta responses in luminal versus mesenchymal human breast cancer cells. Breast Cancer Res, 2005, 7(6), R1058-1079.
65. Joshi, J.P.; Brown, N.E.; Griner, S.E.; Nahta, R. Growth differentiation factor 15 (GDF15)-mediated HER2 phosphorylation reduces trastuzumab sensitivity of HER2-overexpressing breast cancer cells. Biochem Pharmacol, 2011, 82(9), 1090-1099.
66. Kim, K.K.; Lee, J.J.; Yang, Y.; You, K.H.; Lee, J.H. Macrophage inhibitory cytokine-1 activates AKT and ERK-1/2 via the transactivation of ErbB2 in human breast and gastric cancer cells. Carcinogenesis, 2008, 29(4), 704-712.
67. Park, Y.J.; Lee, H.; Lee, J.H. Macrophage inhibitory cytokine-1 transactivates ErbB family receptors via the activation of Src in SK-BR-3 human breast cancer cells. BMB Rep, 2010, 43(2), 91-96.
68. Berns, K.; Horlings, H.M.; Hennessy, B.T.; Madiredjo, M.; Hijmans, E.M.; Beelen, K.; Linn, S.C.; Gonzalez-Angulo, A.M.; Stemke-Hale, K.; Hauptmann, M.; Beijersbergen, R.L.; Mills, G.B.; van de Vijver, M.J.; Bernards, R. A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell, 2007, 12(4), 395-402. (Pubitemid 47539306)
69. Nagata, Y.; Lan, K.H.; Zhou, X.; Tan, M.; Esteva, F.J.; Sahin, A.A.; Klos, K.S.; Li, P.; Monia, B.P.; Nguyen, N.T.; Hortobagyi, G.N.; Hung, M.C.; Yu, D. PTEN activation contributes to tumor inhibition by trastuzumab, and lossof PTEN predicts trastuzumab resistance in patients. Cancer Cell, 2004, 6(2), 117-127. (Pubitemid 39485684)
70. Lu, C.H.; Wyszomierski, S.L.; Tseng, L.M.; Sun, M.H.; Lan, K.H.; Neal, C.L.; Mills, G.B.; Hortobagyi, G.N.; Esteva, F.J.; Yu, D. Preclinical testing of clinically applicable strategies for overcoming trastuzumab resistance caused by PTEN deficiency. Clin Cancer Res, 2007, 13(19), 5883-5888. (Pubitemid 47583915)
71. Ozbay, T.; Durden, D.L.; Liu, T.; O'Regan, R.M.; Nahta, R. In vitro evaluation of pan-PI3-kinase inhibitor SF1126 in trastuzumab-sensitive and trastuzumab-resistant HER2-over-expressing breast cancer cells. Cancer Chemother Pharmacol, 2010, 65(4), 697-706.
72. Garlich, J.R.; De, P.; Dey, N.; Su, J.D.; Peng, X.; Miller, A.; Murali, R.; Lu, Y.; Mills, G.B.; Kundra, V.; Shu, H.K.; Peng, Q.; Durden, D.L. A vascular targeted pan phosphoinositide 3-kinase inhibitor prodrug, SF1126, with antitumor and antiangiogenic activity. Cancer Res, 2008, 68(1), 206-215. (Pubitemid 351380122)
73. Crawford, A.; Nahta, R. Targeting Bcl-2 in Herceptin-Resistant Breast Cancer Cell Lines. Current pharmacogenomics and personalized medicine, 2011, 9(3), 184-190.
74. Andre, F.; Campone, M.; O'Regan, R.; Manlius, C.; Massacesi, C.; Sahmoud, T.; Mukhopadhyay, P.; Soria, J.C.; Naughton, M.; Hurvitz, S.A. Phase I study of everolimus plus weekly paclitaxel and trastuzumab in patients with metastatic breast cancer pretreated with trastuzumab. J Clin Oncol, 2010, 28(34), 5110-5115.
75. Yardley, D.S., M.; Ray-Coquard, I.; Melichar, B.; Hart, L.; Dieras, V.; Barve, M.; Melnyk, A.; Dorer, D.; Turner, C.; Dodion, P. In Cancer Res, Proceedings of the 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium, Ridaforolimus (AP23573; MK-8669) in Combination with Trastuzumab for Patients with HER2-Positive Trastuzumab-Refractory Metastatic Breast Cancer: A Multicenter Phase 2 Clinical Trial.: 2009; p 3091.
76. Baselga, J.B., I.; Eidtmann, H.; Di Cosimo, S.; Aura, C.; De Azambuja, E.; Gomez, H.; Dinh, P.; Fauria, K.; Van Dooren, V.; Paoletti, P.; Goldhirsch, A.; Chang, T-W.; Lang, I.; Untch, M.; Gelber, R. D.; Piccart-Gebhart, M.; on Behalf of the NeoALTTO Study Team. In Cancer Res, Proceedings of the Thirty-Third Annual CTRC-AACR San Antonio Breast Cancer Symposium, First Results of the NeoALTTO Trial (BIG 01-06/EGF 106903): A Phase III, Randomized, Open Label, Neoadjuvant Study of Lapatinib, Trastuzumab, and Their Combination Plus Paclitaxel in Women with HER2-Positive Primary Breast Cancer.: 2010; pp S3-3.
77. Jerusalem, G.; Fasolo, A.; Dieras, V.; Cardoso, F.; Bergh, J.; Vittori, L.; Zhang, Y.; Massacesi, C.; Sahmoud, T.; Gianni, L. Phase I trial of oral mTOR inhibitor everolimus in combination with trastuzumab and vinorelbine in pre-treated patients with HER2-overexpressing metastatic breast cancer. Breast Cancer Res Treat, 2011, 125(2), 447-455.
78. Morrow, P.K.; Wulf, G.M.; Ensor, J.; Booser, D.J.; Moore, J.A.; Flores, P.R.; Xiong, Y.; Zhang, S.; Krop, I.E.; Winer, E.P.; Kindelberger, D.W.; Coviello, J.; Sahin, A.A.; Nunez, R.; Hortobagyi, G.N.; Yu, D.; Esteva, F.J. Phase I/II study of trastuzumab in combination with everolimus (RAD001) in patients with HER2-overexpressing metastatic breast cancer who progressed on trastuzumab-based therapy. J Clin Oncol, 2011, 29(23), 3126-3132.
79. Nahta, R.; O'Regan, R.M. Evolving strategies for overcoming resistance to HER2-directed therapy: targeting the PI3K/Akt/mTOR pathway. Clin Breast Cancer, 2010, 10 Suppl 3, S72-78.
80. Xia, W.; Husain, I.; Liu, L.; Bacus, S.; Saini, S.; Spohn, J.; Pry, K.; Westlund, R.; Stein, S.H.; Spector, N.L. Lapatinib antitumor activity is not dependent upon phosphatase and tensin homologue deleted on chromosome 10 in ErbB2-overexpressing breast cancers. Cancer Res, 2007, 67(3), 1170-1175.
81. Gayle, S.S.; Arnold, S.L.; O'Regan, R.M.; Nahta, R. Pharmacologic Inhibition of mTOR Improves Lapatinib Sensitivity in HER2-Overexpressing Breast Cancer Cells with Primary Trastuzumab Resistance. Anti-cancer agents in medicinal chemistry, 2011,
82. Vadlamudi, R.K.; Adam, L.; Nguyen, D.; Santos, M.; Kumar, R. Differential regulation of components of the focal adhesion complex by heregulin: role of phosphatase SHP-2. J Cell Physiol, 2002, 190(2), 189-199. (Pubitemid 34027821)
83. Vadlamudi, R.K.; Sahin, A.A.; Adam, L.; Wang, R.A.; Kumar, R. Heregulin and HER2 signaling selectively activates c-Src phosphorylation at tyrosine 215. FEBS Lett, 2003, 543(1-3), 76-80. (Pubitemid 36577231)
84. Schmitz, K.J.; Grabellus, F.; Callies, R.; Otterbach, F.; Wohlschlaeger, J.; Levkau, B.; Kimmig, R.; Schmid, K.W.; Baba, H.A. High expression of focal adhesion kinase (p125FAK) in node-negative breast cancer is related to overexpression of HER-2/neu and activated Akt kinase but does not predict outcome. Breast Cancer Res, 2005, 7(2), R194-203.
85. Wang, S.E.; Xiang, B.; Zent, R.; Quaranta, V.; Pozzi, A.; Arteaga, C.L. Transforming growth factor beta induces clustering of HER2 and integrins by activating Src-focal adhesion kinase and receptor association to the cytoskeleton. Cancer Res, 2009, 69(2), 475-482.
86. Yang, X.H.; Flores, L.M.; Li, Q.; Zhou, P.; Xu, F.; Krop, I.E.; Hemler, M.E. Disruption of laminin-integrin-CD151-focal adhesion kinase axis sensitizes breast cancer cells to ErbB2 antagonists. Cancer Res, 2010, 70(6), 2256-2263.
87. Huang, C.; Park, C.C.; Hilsenbeck, S.G.; Ward, R.; Rimawi, M.F.; Wang, Y.C.; Shou, J.; Bissell, M.J.; Osborne, C.K.; Schiff, R. beta1 integrin mediates an alternative survival pathway in breast cancer cells resistant to lapatinib. Breast Cancer Res, 2011, 13(4), R84.
88. Shi, Q.; Hjelmeland, A.B.; Keir, S.T.; Song, L.; Wickman, S.; Jackson, D.; Ohmori, O.; Bigner, D.D.; Friedman, H.S.; Rich, J.N. A novel low-molecular weight inhibitor of focal adhesion kinase, TAE226, inhibits glioma growth. Mol Carcinog, 2007, 46(6), 488-496. (Pubitemid 46897053)
89. Golubovskaya, V.M.; Virnig, C.; Cance, W.G. TAE226-induced apoptosis in breast cancer cells with overexpressed Src or EGFR. Mol Carcinog, 2008, 47(3), 222-234. (Pubitemid 351398065)
90. Wang, Z.G.; Fukazawa, T.; Nishikawa, T.; Watanabe, N.; Sakurama, K.; Motoki, T.; Takaoka, M.; Hatakeyama, S.; Omori, O.; Ohara, T.; Tanabe, S.; Fujiwara, Y.; Shirakawa, Y.; Yamatsuji, T.; Tanaka, N.; Naomoto, Y. TAE226, a dual inhibitor for FAK and IGF-IR, has inhibitory effects on mTOR signaling in esophageal cancer cells. Oncol Rep, 2008, 20(6), 1473-1477.
91. Liang, K.; Esteva, F.J.; Albarracin, C.; Stemke-Hale, K.; Lu, Y.; Bianchini, G.; Yang, C.Y.; Li, Y.; Li, X.; Chen, C.T.; Mills, G.B.; Hortobagyi, G.N.; Mendelsohn, J.; Hung, M.C.; Fan, Z. Recombinant human erythropoietin antagonizes trastuzumab treatment of breast cancer cells via Jak2-mediated Src activation and PTEN inactivation. Cancer Cell, 2010, 18(5), 423-435.
92. Zhuang, G.; Brantley-Sieders, D.M.; Vaught, D.; Yu, J.; Xie, L.; Wells, S.; Jackson, D.; Muraoka-Cook, R.; Arteaga, C.; Chen, J. Elevation of receptor tyrosine kinase EphA2 mediates resistance to trastuzumab therapy. Cancer Res, 2010, 70(1), 299-308.
93. Zhang, S.; Huang, W.C.; Li, P.; Guo, H.; Poh, S.B.; Brady, S.W.; Xiong, Y.; Tseng, L.M.; Li, S.H.; Ding, Z.; Sahin, A.A.; Esteva, F.J.; Hortobagyi, G.N.; Yu, D. Combating trastuzumab resistance by targeting SRC, a common node downstream of multiple resistance pathways. Nat Med, 2011, 17(4), 461-469.
94. Baselga, J.; Cervantes, A.; Martinelli, E.; Chirivella, I.; Hoekman, K.; Hurwitz, H.I.; Jodrell, D.I.; Hamberg, P.; Casado, E.; Elvin, P.; Swaisland, A.; Iacona, R.; Tabernero, J. Phase I safety, pharmacokinetics, and inhibition of SRC activity study of saracatinib in patients with solid tumors. Clin Cancer Res, 2010, 16(19), 4876-4883.
95. Mayer, E.; Baurain, J.F.; Sparano, J.A.; Strauss, L.C.; Campone, M.; Fumoleau, P.; Rugo, H.; Awada, A.; Sy, O.; Llombart-Cussac, A. A phase 2 trial of dasatinib in patients with advanced HER2-positive and/or hormone receptor-positive breast cancer. Clin Cancer Res, 2011,
96. Spigel, D.R.; Hainsworth, J.D.; Burris, H.A., 3rd; Molthrop, D.C.; Peacock, N.; Kommor, M.; Vazquez, E.R.; Greco, F.A.; Yardley, D.A. A pilot study of adjuvant doxorubicin and cyclophosphamide followed by paclitaxel and sorafenib in women with node-positive or high-risk early-stage breast cancer. Clinical advances in hematology & oncology : H&O, 2011, 9(4), 280-286.
97. Isaacs, C.; Herbolsheimer, P.; Liu, M.C.; Wilkinson, M.; Ottaviano, Y.; Chung, G.G.; Warren, R.; Eng-Wong, J.; Cohen, P.; Smith, K.L.; Creswell, K.; Novielli, A.; Slack, R. Phase I/II study of sorafenib with anastrozole in patients with hormone receptor positive aromatase inhibitor resistant metastatic breast cancer. Breast Cancer Res Treat, 2011, 125(1), 137-143.
98. Mayer, E.L.; Baurain, J.F.; Sparano, J.; Strauss, L.; Campone, M.; Fumoleau, P.; Rugo, H.; Awada, A.; Sy, O.; Llombart-Cussac, A. A phase 2 trial of dasatinib in patients with advanced HER2-positive and/or hormone receptor-positive breast cancer. Clin Cancer Res, 2011, 17(21), 6897-6904.
99. 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(24), 1852-1857. (Pubitemid 34048651)