Drug target strategies in breast cancer treatment: Recent developments

Anti-Cancer Agents in Medicinal Chemistry

Volumn 14, Issue 10, 2014, Pages 1414-1427

  Mayank, ^a   Jaitak, Vikas ^a  

^a CENTRAL UNIVERSITY OF PUNJAB   (India)

Author keywords

Breast cancer; Chemotherapy; Crosstalk; Resistance; Targeting

Indexed keywords

CD3 ANTIGEN; COLLAGENASE; CYCLIN D1; EPIDERMAL GROWTH FACTOR RECEPTOR; ESTROGEN RECEPTOR; FULVESTRANT; G PROTEIN COUPLED RECEPTOR 30; HEAT SHOCK PROTEIN; HEPATOCYTE NUCLEAR FACTOR 3ALPHA; HISTONE DEACETYLASE; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; MILTEFOSINE; MITOGEN ACTIVATED PROTEIN KINASE 1; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN ARGININE METHYLTRANSFERASE; PROTEIN PS2; PROTEIN SERINE THREONINE KINASE; RALOXIFENE; SOMATOMEDIN C; SOMATOMEDIN C RECEPTOR; STEROID RECEPTOR COACTIVATOR 1; SYNAPSIN I; TAMOXIFEN; TRANSCRIPTION FACTOR PAX2; TRANSFORMING GROWTH FACTOR ALPHA; VASCULOTROPIN; ANTINEOPLASTIC AGENT; EGFR PROTEIN, HUMAN; ENZYME INHIBITOR; HISTONE DEACETYLASE INHIBITOR; MTOR PROTEIN, HUMAN; TARGET OF RAPAMYCIN KINASE;

ARTICLE; BREAST CANCER; CANCER THERAPY; CELL PROLIFERATION; DOWN REGULATION; EPITHELIAL MESENCHYMAL TRANSITION; ESTROGEN RESPONSIVE ELEMENT; ESTROGEN THERAPY; GENE CONTROL; GENE EXPRESSION; HUMAN; MOLECULARLY TARGETED THERAPY; NONHUMAN; SIGNAL TRANSDUCTION; TUMOR REGRESSION; UPREGULATION; WNT SIGNALING PATHWAY; ANTAGONISTS AND INHIBITORS; BREAST NEOPLASMS; DRUG RESISTANCE; FEMALE; METABOLISM;

ANTINEOPLASTIC AGENTS; BREAST NEOPLASMS; DRUG RESISTANCE, NEOPLASM; ENZYME INHIBITORS; FEMALE; HISTONE DEACETYLASE INHIBITORS; HISTONE DEACETYLASES; HUMANS; MOLECULAR TARGETED THERAPY; POLY(ADP-RIBOSE) POLYMERASES; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTORS, ESTROGEN; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES;

EID: 84935423856     PISSN: 18715206     EISSN: 18755992     Source Type: Journal    
DOI: 10.2174/1871520614666140407114853     Document Type: Article

References (157)

1. Gangopadhyay, S.; Nandy, A.; Hor, P.; Mukhopadhyay, A. Breast cancer stem cells: A novel therapeutic target. Clin. Breast Cancer, 2013, 13(1), 7-15.
2. Siegel, R.; Naishadham, D.; Jemal, A. Cancer statistics, 2013. CACancer J. Clin., 2013, 63(1), 11-30.
3. Martin, A.M.; Weber, B.L. Genetic and hormonal risk factors in breast cancer. J. Natl. Cancer I., 2000, 92(14), 1126-1135.
4. Chen, J.Q.; Russo, J. ERα-negative and triple negative breast cancer: Molecular features and potential therapeutic approaches. BBA-Rev. Cancer, 2009, 1796(2), 162-175.
5. Higgins, M.J.; Baselga, J. Targeted therapies for breast cancer. J. Clin. Invest., 2011, 121(10), 3797-3803.
6. Ko, J.H.; Ko, E.A.; Gu, W.; Lim, I.; Bang, H.; Zhou, T. Expression profiling of ion channel genes predicts clinical outcome in breast cancer. Mol. Cancer, 2013, 12(1), 106.
7. Konecny, G.E.; Pegram, M.D.; Venkatesan, N.; Finn, R.; Yang, G.; Rahmeh, M.; Untch, M.; Rusnak, D.W.; Spehar, G.; Mullin, R.J. Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. Cancer Res., 2006, 66(3), 1630-1639.
8. Lawler, P.; Miao, W.; Williams, P. From the Editor’s Desk: The emergence of "personalized medicine" in medical care. MJM, 2007, 10 (1), 1.
9. Ismail-Khan, R.; Bui, M.M. A review of triple-negative breast cancer. Cancer Cont., 2010, 17(3), 173-176.
10. Kao, J.; Salari, K.; Bocanegra, M.; Choi, Y.L.; Girard, L.; Gandhi, J.; Kwei, K.A.; Hernandez-Boussard, T.; Wang, P.; Gazdar, A.F. Molecular profiling of breast cancer cell lines defines relevant tumor models and provides a resource for cancer gene discovery. PloS One, 2009, 4(7), e6146.
11. Osborne, C.K.; Shou, J.; Massarweh, S.; Schiff, R. Crosstalk between estrogen receptor and growth factor receptor pathways as a cause for endocrine therapy resistance in breast cancer. Clin. Cancer Res., 2005, 11(2), 865s-870s.
12. Manavathi, B.; Dey, O.; Gajulapalli, V.N.R.; Bhatia, R.S.; Bugide, S.; Kumar, R. Derailed estrogen signaling and breast cancer: An authentic couple. Endocr. Rev., 2012, 34 (1), 1-32.
13. Beatson, G. On the treatment of inoperable cases of carcinoma of the mamma: Suggestions for a new method of treatment, with illustrative cases. The Lancet, 1896, 148(3802), 104-107.
14. Renoir, J.M. Estradiol receptors in breast cancer cells: Associated co-factors as targets for new therapeutic approaches. Steroids, 2012, 77(12), 1249-1261.
15. Palmieri, C.; Cheng, G.; Saji, S.; Zelada-Hedman, M.; Weihua, Z.; Van Noorden, S.; Wahlstrom, T.; Coombes, R.; Warner, M.; Gustafsson, J. Estrogen receptor beta in breast cancer. Endocr-Relat. Cancer, 2002, 9(1), 1-13.
16. Paruthiyil, S.; Parmar, H.; Kerekatte, V.; Cunha, G.R.; Firestone, G.L.; Leitman, D.C. Estrogen receptor β inhibits human breast cancer cell proliferation and tumor formation by causing a G2 cell cycle arrest. Cancer Res., 2004, 64(1), 423-428.
17. Kumar, V.; Green, S.; Stack, G.; Berry, M.; Jin, J.R.; Chambon, P. Functional domains of the human estrogen receptor. Cell, 1987, 51(6), 941-951.
18. Renoir, J.M.; Radanyi, C.; Faber, L.; Baulieu, E.E. The non-DNAbinding heterooligomeric form of mammalian steroid hormone receptors contains a hsp90-bound 59-kilodalton protein. J. Biol. Chem., 1990, 265(18), 10740-10745.
19. Segnitz, B.; Gehring, U. Subunit structure of the nonactivated human estrogen receptor. P. Natl. A. Sci. USA, 1995, 92(6), 2179-2183.
20. Pratt, W.B. The role of Thehsp90-based chaperone system in signal transduction by nuclear receptors and receptors signaling via map kinase. Annu. Rev. Pharmacol., 1997, 37 (1), 297-326.
21. Klein-Hitpas, L.; Schorpp, M.; Wagner, U.; Ryffel, G.U. An estrogen-responsive element derived from the 5′ flanking region of the Xenopus vitellogenin A2 gene functions in transfected human cells. Cell, 1986, 46 (7), 1053-1061.
22. Frasor, J.; Danes, J.M.; Komm, B.; Chang, K.C.; Lyttle, C.R.; Katzenellenbogen, B.S. Profiling of estrogen up-and downregulated gene expression in human breast cancer cells: Insights into gene networks and pathways underlying estrogenic control of proliferation and cell phenotype. Endocrinology, 2003, 144(10), 4562-4574.
23. Rosenfeld, M.G.; Glass, C.K. Coregulator codes of transcriptional regulation by nuclear receptors. J. Biol. Chem., 2001, 276(40), 36865-36868.
24. Moriarty, K.; Kim, K.; Bender, J. Estrogen receptor-mediated rapid signaling. Endocrinology, 2006, 147(12), 5557-5563.
25. Thomas, P.; Pang, Y.; Filardo, E.; Dong, J. Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells. Endocrinology, 2005, 146(2), 624-632.
26. Zhou, Z.; Qiao, J.; Shetty, A.; Wu, G.; Huang, Y.; Davidson, N.; Wan, Y. Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy. Cell. Mol. Life. Sci., 2013, 1-1.
27. Acconcia, F.; Ascenzi, P.; Bocedi, A.; Spisni, E.; Tomasi, V.; Trentalance, A.; Visca, P.; Marino, M. Palmitoylation-dependent estrogen receptor α membrane localization: Regulation by 17β- estradiol. Mol. Biol. Cell, 2005, 16(1), 231-237.
28. Le Romancer, M.; Treilleux, I.; Leconte, N.; Robin-Lespinasse, Y.; Sentis, S.; Bouchekioua-Bouzaghou, K.; Goddard, S.; Gobert-Gosse, S.; Corbo, L. Regulation of estrogen rapid signaling through arginine methylation by PRMT1. Mol. Cell, 2008, 31(2), 212-221.
29. Conzen, S.D. Minireview: Nuclear receptors and breast cancer. Mol. Endocrinol., 2008, 22(10), 2215-2228.
30. Kim, R.; Kaneko, M.; Arihiro, K.; Emi, M.; Tanabe, K.; Murakami, S.; Osaki, A.; Inai, K. Extranuclear expression of hormone receptors in primary breast cancer. Ann. Oncol., 2006, 17(8), 1213-1220.
31. Acconcia, F.; Manavathi, B.; Mascarenhas, J.; Talukder, A.H.; Mills, G.; Kumar, R. An inherent role of integrin-linked kinaseestrogen receptor α interaction in cell migration. Cancer Res., 2006, 66(22), 11030-11038.
32. Azuma, K.; Urano, T.; Horie-Inoue, K.; Hayashi, S.I.; Sakai, R.; Ouchi, Y.; Inoue, S. Association of estrogen receptor α and histone deacetylase 6 causes rapid deacetylation of tubulin in breast cancer cells. Cancer Res., 2009, 69(7), 2935-2940.
33. Fernando, R.I.; Wimalasena, J.Estradiol abrogates apoptosis in breast cancer cells through inactivation of BAD: Ras-dependent nongenomic pathways requiring signaling through ERK and Akt. Mol. Biol. Cell, 2004, 15(7), 3266-3284.
34. Shou, J.; Massarweh, S.; Osborne, C.K.; Wakeling, A.E.; Ali, S.; Weiss, H.; Schiff, R. Mechanisms of tamoxifen resistance: Increased estrogen receptor-HER2/neu cross-talk in ER/HER2- positive breast cancer. J. Natl Cancer I, 2004, 96(12), 926-935.
35. Migliaccio, A.; Di Domenico, M.; Castoria, G.; De Falco, A.; Bontempo, P.; Nola, E.; Auricchio, F. Tyrosine kinase/p21ras/ MAP-kinase pathway activation by estradiol-receptor complex in MCF-7 cells. EMBO J, 1996, 15(6), 1292-1300.
36. Kahlert, S.; Nuedling, S.; Van Eickels, M.; Vetter, H.; Meyer, R.; Grohe, C. Estrogen receptor α rapidly activates the IGF-1 receptor pathway. J. Biol. Chem., 2000, 275(24), 18447-18453.
37. Chung, Y.L.; Sheu, M.L.; Yang, S.C.; Lin, C.H.; Yen, S.H. Resistance to tamoxifen_induced apoptosis is associated with direct interaction between HER2/neu and cell membrane estrogen receptor in breast cancer. Int. J. Cancer, 2002, 97(3), 306-312.
38. Wong, C.W.; McNally, C.; Nickbarg, E.; Komm, B.S.; Cheskis, B. J. Estrogen receptor-interacting protein that modulates its nongenomic activity-crosstalk with Src/Erk phosphorylation cascade. P. Natl. A. Sci. USA., 2002, 99(23), 14783-14788.
39. Schiff, R.; Massarweh, S.A.; Shou, J.; Bharwani, L.; Mohsin, S.K.; Osborne, C.K. Cross-talk between estrogen receptor and growth factor pathways as a molecular target for overcoming endocrine resistance. Clin. Cancer Res., 2004, 10(1), 331s-336s.
40. Bunone, G.; Briand, P.; Miksicek, R.; Picard, D. Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation. EMBO J., 1996, 15(9), 2174.
41. De Mora, J.F.; Brown, M. AIB1 is a conduit for kinase-mediated growth factor signaling to the estrogen receptor. Mol. Cell. Biol., 2000, 20(14), 5041-5047.
42. Campbell, R.A.; Bhat-Nakshatri, P.; Patel, N.M.; Constantinidou, D.; Ali, S.; Nakshatri, H. Phosphatidylinositol 3-Kinase/AKTmediated Activation of Estrogen Receptor α a new model for antiestrogen resistance. J. Biol. Chem., 2001, 276(13), 9817-9824.
43. Levin, E.R. Bidirectional signaling between the estrogen receptor and the epidermal growth factor receptor. Mol. Endocrinol., 2003, 17(3), 309-317.
44. Goss, P.E.; Strasser, K. Aromatase inhibitors in the treatment and prevention of breast cancer. J. Clin. Oncol., 2001, 19(3), 881-894.
45. Lerner, L.J.; Jordan, V.C. Development of antiestrogens and their use in breast cancer: Eighth Cain memorial award lecture. Cancer Res., 1990, 50(14), 4177-4189.
46. King, M.C.; Wieand, S.; Hale, K.; Lee, M.; Walsh, T.; Owens, K.; Tait, J.; Ford, L.; Dunn, B.K.; Costantino, J. Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. Jama, 2001, 286(18), 2251-2256.
47. Lorraine, J., Raloxifene and breast cancer. Can. Med. Assoc. J., 2001, 165(7), 888-888.
48. Cuzick, J.; DeCensi, A.; Arun, B.; Brown, P.H.; Castiglione, M.; Dunn, B.; Forbes, J.F.; Glaus, A.; Howell, A.; Von Minckwitz, G. Preventive therapy for breast cancer: A consensus statement. Lancet. Oncol., 2011, 12(5), 496-503.
49. Howell, S.J.; Johnston, S.R.; Howell, A. The use of selective estrogen receptor modulators and selective estrogen receptor downregulators in breast cancer. Best Pract. Res. Clin. En., 2004, 18(1), 47-66.
50. Howell, A.; Robertson, J.F.; Abram, P.; Lichinitser, M.R.; Elledge, R.; Bajetta, E.; Watanabe, T.; Morris, C.; Webster, A.; Dimery, I. Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: A multinational, double-blind, randomized trial. J. Clin. Oncol., 2004, 22(9), 1605-1613.
51. Osborne, C.; Wakeling, A.; Nicholson, R. Fulvestrant: An oestrogen receptor antagonist with a novel mechanism of action. Brit. J. Cancer, 2004, 90, S2-S6.
52. Adelson, K.; Germain, D.; Raptis, G.; Biran, N. Hormonal modulation in the treatment of breast cancer. Endocrin. Metab. Clin., 2011, 40(3), 519-532.
53. Nabholtz, J.; Buzdar, A.; Pollak, M.; Harwin, W.; Burton, G.; Mangalik, A.; Steinberg, M.; Webster, A.; Von Euler, M. Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: Results of a North American multicenter randomized trial. J. Clin. Oncol., 2000, 18(22), 3758-3767.
54. Rinaldi, R.Z. Aromatase Inhibitor Adjuvant Chemotherapy of Breast Cancer Results in Cancer Therapy Induced Bone Loss. Curr. Osteoporos. Rep., 2013, 11(1), 61-64.
55. Thurlimann, B.; Paridaens, R.; Serin, D.; Bonneterre, J.; Murray, R.; Salle, E.D.; Lanzalone, S.; Zurlo, M.; Piscitelli, G. Third-line hormonal treatment with exemestane in postmenopausal patients with advanced breast cancer progressing on aminoglutethimide: A phase II multicentre multinational study. Eur. J. Cancer., 1997, 33(11), 1767-1773.
56. Bertelli, G.; Hall, E.; Ireland, E.; Snowdon, C.; Jassem, J.; Drosik, K.; Karnicka-Mlodkowska, H.; Coombes, R.; Bliss, J. Long-term endometrial effects in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES)a randomised controlled trial of exemestane versus continued tamoxifen after 2-3 years tamoxifen. Ann. Oncol., 2010, 21(3), 498-505.
57. Hartman, J.; Lindberg, K.; Morani, A.; Inzunza, J.; Strom, A.; Gustafsson, J.A. Estrogen receptor β inhibits angiogenesis and growth of T47D breast cancer xenografts. Cancer Res., 2006, 66(23), 11207-11213.
58. Loveday, R.L.; Greenman, J.; Simcox, D.L.; Speirs, V.; Drew, P. J.; Monson, J.R.; Kerin, M.J. Genetic changes in breast cancer detected by comparative genomic hybridisation. Int. J. Cancer, 2000, 86(4), 494-500.
59. Burki, N.G.; Caduff, R.; Walt, H.; Moll, C.; Pejovic, T.; Haller, U.; Ward, D.C. Comparative genomic hybridization of fine needle aspirates from breast carcinomas. Int. J. Cancer., 2000, 88(4), 607-613.
60. Stettner, M.; Kaulfus, S.; Burfeind, P.; Schweyer, S.; Strauss, A.; Ringert, R.H.; Thelen, P. The relevance of estrogen receptor-β expression to the antiproliferative effects observed with histone deacetylase inhibitors and phytoestrogens in prostate cancer treatment. Mol. Cancer Ther., 2007, 6(10), 2626-2633.
61. Treeck, O.; Juhasz-Boess, I.; Lattrich, C.; Horn, F.; Goerse, R.; Ortmann, O. Effects of exon-deleted estrogen receptor β transcript variants on growth, apoptosis and gene expression of human breast cancer cell lines. Breast Cancer Res. Tr., 2008, 110(3), 507-520.
62. Frasor, J.; Chang, E.C.; Komm, B.; Lin, C.Y.; Vega, V.B.; Liu, E. T.; Miller, L.D.; Smeds, J.; Bergh, J.; Katzenellenbogen, B.S. Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. Cancer Res., 2006, 66(14), 7334-7340.
63. Chang, E.C.; Frasor, J.; Komm, B.; Katzenellenbogen, B.S. Impact of estrogen receptor β on gene networks regulated by estrogen receptor α in breast cancer cells. Endocrinology, 2006, 147(10), 4831-4842.
64. Levy, N.; Paruthiyil, S.; Zhao, X.; Vivar, O.I.; Saunier, E.F.; Griffin, C.; Tagliaferri, M.; Cohen, I.; Speed, T.P.; Leitman, D.C. Unliganded estrogen receptor-β regulation of genes is inhibited by tamoxifen. Mol. Cell. Endocrinol., 2010, 315(1), 201-207.
65. Chen, W.; Lin, Z.; Ning, M.; Yang, C.; Yan, X.; Xie, Y.; Shen, X.; Wang, M.W. Aza analogues of equol: Novel ligands for estrogen receptor β. Bioorgan. Med. Chem., 2007, 15(17), 5828-5836.
66. Lappano, R.; Santolla, M.F.; Pupo, M.; Sinicropi, M.S.; Caruso, A.; Rosano, C.; Maggiolini, M. MIBE acts as antagonist ligand of both estrogen receptor α and GPER in breast cancer cells. Breast Cancer Res., 2012, 14(1), R12.
67. Albanito, L.; Sisci, D.; Aquila, S.; Brunelli, E.; Vivacqua, A.; Madeo, A.; Lappano, R.; Pandey, D.P.; Picard, D.; Mauro, L. Epidermal growth factor induces G protein-coupled receptor 30 expression in estrogen receptor-negative breast cancer cells. Endocrinology, 2008, 149(8), 3799-3808.
68. Dennis, M.K.; Field, A.S.; Burai, R.; Ramesh, C.; Petrie, W.K.; Bologa, C.G.; Oprea, T.I.; Yamaguchi, Y.; Hayashi, S. I.; Sklar, L. A. Identification of a GPER/GPR30 antagonist with improved estrogen receptor counterselectivity. J. Steroid Biochem. Mol. Biol., 2011, 127(3), 358-366.
69. Chauchereau, A.; Amazit, L.; Quesne, M.; Guiochon-Mantel, A.; Milgrom, E. Sumoylation of the progesterone receptor and of the steroid receptor coactivator SRC-1. J. Biol. Chem., 2003, 278(14), 12335-12343.
70. O’Malley, B.W.; Kumar, R. Nuclear receptor coregulators in cancer biology. Cancer Res., 2009, 69(21), 8217-8222.
71. Lonard, D.M.; Lanz, R.B.; O’Malley, B.W. Nuclear receptor coregulators and human disease. Endocr. Rev., 2007, 28(5), 575-587.
72. Dobrzycka, K.; Townson, S.; Jiang, S.; Oesterreich, S. Estrogen receptor corepressors--a role in human breast cancer? Endocr-Relat. Cancer, 2003, 10(4), 517-536.
73. Walsh, C.A.; Qin, L.; Tien, J.; Young, L.S.; Xu, J. The function of steroid receptor coactivator-1 in normal tissues and cancer. Int. J. Biol. Sci., 2012, 8(4), 470-485.
74. Xu, J.; Li, Q. Review of the in vivo functions of the p160 steroid receptor coactivator family. Mol. Endocrinol., 2003, 17(9), 1681-1692.
75. Tai, H.; Kubota, N.; Kato, S. Involvement of nuclear receptor coactivator SRC-1 in estrogen-dependent cell growth of MCF-7 cells. Biochem. Bioph. Res. Co., 2000, 267(1), 311-316.
76. Kishimoto, H.; Wang, Z.; Bhat-Nakshatri, P.; Chang, D.; Clarke, R.; Nakshatri, H. The p160 family coactivators regulate breast cancer cell proliferation and invasion through autocrine/paracrine activity of SDF-1α/CXCL12. Carcinogenesis, 2005, 26(10), 1706-1715.
77. Qin, L.; Liu, Z.; Chen, H.; Xu, J. The steroid receptor coactivator-1 regulates twist expression and promotes breast cancer metastasis. Cancer Res., 2009, 69(9), 3819-3827.
78. Fenne, I.S.; Helland, T.; Flageng, M.H.; Dankel, S.N.; Mellgren, G.; Sagen, J.V. Downregulation of steroid receptor coactivator-2 modulates estrogen-responsive genes and stimulates proliferation of MCF-7 breast cancer cells. PloS One, 2013, 8(7), e70096.
79. Yan, F.; Wu, S. SRC-3: A transcriptional coactivator and therapeutic target in cancer. J. Postdoc. Res., 2013, 22, 34.
80. Wang, Y.; Lonard, D.M.; Yu, Y.; Chow, D.C.; Palzkill, T.G.; O’Malley, B.W. Small molecule inhibition of the steroid receptor coactivators, SRC-3 and SRC-1. Mol. Endocrinol., 2011, 25(12), 2041-2053.
81. Torres-Arzayus, M.I.; De Mora, J.F.; Yuan, J.; Vazquez, F.; Bronson, R.; Rue, M.; Sellers, W.R.; Brown, M. High tumor incidence and activation of the PI3K/AKT pathway in transgenic mice define AIB1 as an oncogene. Cancer Cell 2004, 6(3), 263-274.
82. Lin, J.; Wu, Y.; Yang, D.; Zhao, Y. Induction of apoptosis and antitumor effects of a small molecule inhibitor of Bcl-2 and Bcl-xl, gossypol acetate, in multiple myeloma in vitro and in vivo. Oncol. Rep., 2013, 30(2), 731-738.
83. Marks, P.A.; Richon, V.M.; Rifkind, R.A. Histone deacetylase inhibitors: Inducers of differentiation or apoptosis of transformed cells. J. Natl. Cancer I, 2000, 92(15), 1210-1216.
84. Minucci, S.; Pelicci, P.G. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat. Rev. Cancer, 2006, 6(1), 38-51.
85. Grayson, D.R.; Kundakovic, M.; Sharma, R.P. Is there a future for histone deacetylase inhibitors in the pharmacotherapy of psychiatric disorders? Mol. Parmacol., 2010, 77(2), 126-135.
86. Kawai, H.; Li, H.; Avraham, S.; Jiang, S.; Avraham, H.K. Overexpression of histone deacetylase HDAC1 modulates breast cancer progression by negative regulation of estrogen receptor α. Int. J. Cancer, 2003, 107(3), 353-358.
87. Munster, P.N.; Troso-Sandoval, T.; Rosen, N.; Rifkind, R.; Marks, P.A.; Richon, V.M. The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces differentiation of human breast cancer cells. Cancer Res., 2001, 61(23), 8492-8497.
88. Bicaku, E.; Marchion, D.C.; Schmitt, M.L.; Munster, P.N. Selective inhibition of histone deacetylase 2 silences progesterone receptor-mediated signaling. Cancer Res., 2008, 68(5), 1513-1519.
89. Hodges-Gallagher, L.; Valentine, C.D.; El Bader, S.; Kushner, P.J. Inhibition of histone deacetylase enhances the anti-proliferative action of antiestrogens on breast cancer cells and blocks tamoxifeninduced proliferation of uterine cells. Breast Cancer Res. Tr., 2007, 105(3), 297-309.
90. Thomas, S.; Thurn, K.T.; Raha, P.; Chen, S.; Munster, P.N. Efficacy of histone deacetylase and estrogen receptor inhibition in breast cancer cells due to concerted down regulation of Akt. Plos One, 2013, 8(7), e68973.
91. Jang, E.R.; Lim, S.J.; Lee, E.S.; Jeong, G.; Kim, T.Y.; Bang, Y.J.; Lee, J.S. The histone deacetylase inhibitor trichostatin A sensitizes estrogen receptor α -negative breast cancer cells to tamoxifen. Oncogene, 2004, 23(9), 1724-1736.
92. Debeb, B.G.; Lacerda, L.; Xu, W.; Larson, R.; Solley, T.; Atkinson, R.; Sulman, E.P.; Ueno, N.T.; Krishnamurthy, S.; Reuben, J.M. Histone deacetylase inhibitors stimulate dedifferentiation of human breast cancer cells through WNT/β_catenin signaling. Stem Cells, 2012, 30(11), 2366-2377.
93. Bertino, E.M.; Otterson, G.A. Romidepsin: A novel histone deacetylase inhibitor for cancer. Expert Opin. Inv. Drug., 2011, 20(8), 1151-1158.
94. Renoir, J.M.; Marsaud, V.; Lazennec, G. Estrogen receptor signaling as a target for novel breast cancer therapeutics. Biochem. Pharmacl., 2013, 85(4), 449-465.
95. Yang, Y.; Bedford, M.T. Protein arginine methyltransferases and cancer. Nat. Rev. Cancer, 2013, 13(1), 37-50.
96. Tang, J.; Frankel, A.; Cook, R.J.; Kim, S.; Paik, W.K.; Williams, K.R.; Clarke, S.; Herschman, H.R. PRMT1 is the predominant type I protein arginine methyltransferase in mammalian cells. J. Biol. Chem., 2000, 275(11), 7723-7730.
97. Cheng, D.; Yadav, N.; King, R.W.; Swanson, M.S.; Weinstein, E.J.; Bedford, M.T. Small molecule regulators of protein 23899.
98. Ragno, R.; Simeoni, S.; Castellano, S.; Vicidomini, C.; Mai, A.; Caroli, A.; Tramontano, A.; Bonaccini, C.; Trojer, P.; Bauer, I. Small molecule inhibitors of histone arginine methyltransferases: Homology modeling, molecular docking, binding mode analysis, and biological evaluations. J. Med. Chem., 2007, 50(6), 1241-1253.
99. Balasubramanyam, K.; Varier, R.A.; Altaf, M.; Swaminathan, V.; Siddappa, N.B.; Ranga, U.; Kundu, T.K. Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription. J. Biol. Chem., 2004, 279(49), 51163-51171.
100. Mai, A.; Cheng, D.; Bedford, M.T.; Valente, S.; Nebbioso, A.; Perrone, A.; Brosch, G.; Sbardella, G.; De Bellis, F.; Miceli, M. Epigenetic multiple ligands: Mixed histone/protein methyltransferase, acetyltransferase, and class III deacetylase (sirtuin) inhibitors. J. Med. Chem., 2008, 51(7), 2279-2290.
101. Purandare, A.V.; Chen, Z.; Huynh, T.; Pang, S.; Geng, J.; Vaccaro, W.; Poss, M.A.; Oconnell, J.; Nowak, K.; Jayaraman, L. Pyrazole inhibitors of coactivator associated arginine methyltransferase 1 (CARM1). Bioorg. Med. Chem. Lett., 2008, 18(15), 4438-4441.
102. Huynh, T.; Chen, Z.; Pang, S.; Geng, J.; Bandiera, T.; Bindi, S.; Vianello, P.; Roletto, F.; Thieffine, S.; Galvani, A. Optimization of pyrazole inhibitors of coactivator associated arginine methyltransferase 1 (CARM1). Bioorg. Med. Chem. Lett., 2009, 19(11), 2924-2927.
103. Therrien, E.; Larouche, G.; Manku, S.; Allan, M.; Nguyen, N.; Styhler, S.; Robert, M.F.; Goulet, A.C.; Besterman, J.M.; Nguyen, H. 1, 2-Diamines as inhibitors of co-activator associated arginine methyltransferase 1 (CARM1). Bioorg. Med. Chem. Lett., 2009, 19(23), 6725-6732.
104. Yost, J.M.; Korboukh, I.; Liu, F.; Gao, C.; Jin, J. Targets in epigenetics: Inhibiting the methyl writers of the histone code. Curr. Chem. Genomics., 2011, 5 (1) 72-84.
105. Hurtado, A.; Holmes, K.A.; Geistlinger, T.R.; Hutcheson, I.R.; Nicholson, R.I.; Brown, M.; Jiang, J.; Howat, W.J.; Ali, S.; Carroll, J. S. Regulation of ERBB2 by oestrogen receptor-PAX2 determines response to tamoxifen. Nature, 2008, 456 (7222), 663-666.
106. Song, H.; Kwan, S.Y.; Izaguirre, D. I.; Zu, Z.; Tsang, Y.T.; Tung, C.S.; King, E.R.; Mok, S.C.; Gershenson, D.M.; Wong, K.K. PAX2 expression in ovarian cancer. Int. J. Mol. Sci., 2013, 14(3), 6090-6105.
107. Brunquell, C.; Biliran, H.; Jennings, S.; Ireland, S.K.; Chen, R.; Ruoslahti, E. TLE1 Is an anoikis regulator and is downregulated by Bit1 in breast cancer cells. Mol. Cancer Res., 2012, 10(11), 1482-1495.
108. Holmes, K.A.; Hurtado, A.; Brown, G.D.; Launchbury, R.; Ross-Innes, C.S.; Hadfield, J.; Odom, D.T.; Carroll, J.S. Transducin-like enhancer protein 1 mediates estrogen receptor binding and transcriptional activity in breast cancer cells. P. Natl. Acad. Sci. USA, 2012, 109(8), 2748-2753.
109. Lupien, M.; Eeckhoute, J.; Meyer, C.A.; Wang, Q.; Zhang, Y.; Li, W.; Carroll, J.S.; Liu, X.S.; Brown, M. FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription. Cell, 2008, 132(6), 958-970.
110. Fujimori, K.; Amano, F. Forkhead transcription factor Foxa1 is a novel target gene of C/EBPβ and suppresses the early phase of adipogenesis. Gene, 2011, 473(2), 150-156.
111. Kouros-Mehr, H.; Slorach, E.M.; Sternlicht, M.D.; Werb, Z. GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland. Cell, 2006, 127(5), 1041-1055.
112. Badve, S.; Turbin, D.; Thorat, M.A.; Morimiya, A.; Nielsen, T.O.; Perou, C.M.; Dunn, S.; Huntsman, D.G.; Nakshatri, H. FOXA1 expression in breast cancer correlation with luminal subtype A and survival. Clin. Cancer Res., 2007, 13(15), 4415-4421.
113. Hurtado, A.; Holmes, K.A.; Ross-Innes, C.S.; Schmidt, D.; Carroll, J. S. FOXA1 is a key determinant of estrogen receptor function and endocrine response. Nat. Genet., 2011, 43(1), 27-33.
114. Albergaria, A.; Paredes, J.; Sousa, B.; Milanezi, F.; Carneiro, V.; Bastos, J.; Costa, S.; Vieira, D.; Lopes, N.; Lam, E.W. Expression of FOXA1 and GATA-3 in breast cancer: The prognostic significance in hormone receptor-negative tumours. Breast Cancer Res., 2009, 11(3), R40.
115. Sanga, S.; Broom, B.M.; Cristini, V.; Edgerton, M.E. Gene expression meta-analysis supports existence of molecular apocrine breast cancer with a role for androgen receptor and implies interactions with ErbB family. BMC Med. Genomics, 2009, 2(1), 59.
116. Ramamoorthy, S.; Nawaz, Z. E6-associated protein (E6-AP) is a dual function coactivator of steroid hormone receptors. Nucl. Recept. Signal., 2008, 6, e006.
117. Lonard, D.M.; O’Malley, B.W. Nuclear receptor coregulators: Judges, juries, and executioners of cellular regulation. Mol. Cell., 2007, 27(5), 691-700.
118. Gao, X.; Mohsin, S.K.; Gatalica, Z.; Fu, G.; Sharma, P.; Nawaz, Z. Decreased expression of e6-associated protein in breast and prostate carcinomas. Endocrinology, 2005, 146(4), 1707-1712.
119. Ramamoorthy, S.; Tufail, R.; El Hokayem, J.; Jorda, M.; Zhao, W.; Reis, Z.; Nawaz, Z. Overexpression of ligase defective E6-associated protein, E6-AP, results in mammary tumorigenesis. Breast Cancer Res. Tr., 2012, 132(1), 97-108.
120. Nguyen Kovochich, A.; Arensman, M.; Lay, A.R.; Rao, N.P.; Donahue, T.; Li, X.; French, S.W.; Dawson, D.W. HOXB7 promotes invasion and predicts survival in pancreatic adenocarcinoma. Cancer, 2013, 119(3), 529-539.
121. Jin, K.; Kong, X.; Shah, T.; Penet, M.F.; Wildes, F.; Sgroi, D.C.; Ma, X.J.; Huang, Y.; Kallioniemi, A.; Landberg, G. The HOXB7 protein renders breast cancer cells resistant to tamoxifen through activation of the EGFR pathway. P. Natl. Acad. Sci. USA, 2012, 109(8), 2736-2741.
122. Foley, J.; Nickerson, N.K.; Nam, S.; Allen, K.T.; Gilmore, J.L.; Nephew, K.P.; Riese II, D.J. In EGFR signaling in breast cancer: Bad to the bone, Seminars in cell & developmental biology, Elsevier: 2010; pp 951-960.
123. Wicki, A.; Rochlitz, C. Targeted therapies in breast cancer. Swiss Med. Wkly., 2012, 142, w13550.
124. Ellis, M.J.; Tao, Y.; Young, O.; White, S.; Proia, A.D.; Murray, J.; Renshaw, L.; Faratian, D.; Thomas, J.; Dowsett, M. Estrogenindependent proliferation is present in estrogen-receptor HER2- positive primary breast cancer after neoadjuvant letrozole. J. Clin. Oncol., 2006, 24(19), 3019-3025.
125. Rubin, I.; Yarden, Y. The basic biology of HER2. Ann Oncol., 2001, 12 (suppl 1), S3-S8.
126. Ithimakin, S.; Day, K.C.; Malik, F.; Zen, Q.; Dawsey, S.J.; Bersano-Begey, T.F.; Quraishi, A.A.; Ignatoski, K.W.; Daignault, S.; Davis, A. HER2 drives luminal breast cancer stem cells in the absence of HER2 amplification: Implications for efficacy of adjuvant trastuzumab. Cancer Res., 2013, 73(5), 1635-1646.
127. Valabrega, G.; Montemurro, F.; Aglietta, M. Trastuzumab: Mechanism of action, resistance and future perspectives in HER2- overexpressing breast cancer. Ann. Oncol., 2007, 18(6), 977-984.
128. Nahta, R.; Esteva, F.J., Molecular mechanisms of trastuzumab resistance. Breast Cancer Res., 2006, 8(6), 667-674.
129. Krop, I.E.; Beeram, M.; Modi, S.; Jones, S.F.; Holden, S.N.; Yu, W.; Girish, S.; Tibbitts, J.; Yi, J.H.; Sliwkowski, M.X. Phase I study of trastuzumab-DM1, an HER2 antibody-drug conjugate, given every 3 weeks to patients with HER2-positive metastatic breast cancer. J. Clin. Oncol., 2010, 28(16), 2698-2704.
130. Cho, W.C.; Roukos, D.H. Trastuzumab emtansine for advanced HER2-positive breast cancer and beyond: genome landscape-based targets. Exp. Rev. Anticanc., 2013, 13(1), 5-8.
131. Capelan, M.; Pugliano, L.; De Azambuja, E.; Bozovic, I.; Saini, K.; Sotiriou, C.; Loi, S.; Piccart-Gebhart, M. Pertuzumab: New hope for patients with HER2-positive breast cancer. Ann. Oncol., 2013, 2(2), 273-282.
132. Blumenthal, G.M.; Scher, N.S.; Cortazar, P.; Chattopadhyay, S.; Tang, S.; Song, P.; Liu, Q.; Ringgold, K.; Pilaro, A. M.; Tilley, A. First FDA approval of dual anti-HER2 regimen: Pertuzumab in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer. Clin. Cancer Res., 2013, 19(18), 4911-4916.
133. Munster, P.N.; Miller, K.; Krop, I.E.; Dhindsa, N.; Niyikiza, C.; Nielsen, U.; Odueyungbo, A.; Rajarethinmam, A.; Campbell, K.; Geretti, E. In A Phase I study of MM-302, a HER2-targeted liposomal doxorubicin, in patients with advanced, HER2-positive (HER2+) breast cancer, ASCO Annual Meeting. Chicago, IL, USA, 2012; pp 1-5.
134. Kiewe, P.; Hasmuller, S.; Kahlert, S.; Heinrigs, M.; Rack, B.; Marme, A.; Korfel, A.; Jager, M.; Lindhofer, H.; Sommer, H. Phase I trial of the trifunctional anti-HER2× anti-CD3 antibody ertumaxomab in metastatic breast cancer. Clin. Cancer Res., 2006, 12(10), 3085-3091.
135. Richards, D.; Braiteh, F.; Anthony, S.; Edenfield, J.; Hellerstedt, B.; Raju, R.; Conkling, P.; McDonagh, C.; Frye, S.; Moyo, V. A Phase 1 and pharmacologic study of MM-111, a bispecific HER2/HER3 antibody fusion protein, in combination with multiple treatment regimens in patients with advanced HER2 positive solid tumors. Breast, 2012, 20(63), 63.
136. Johnston, S.R.; Gomez, H.; Stemmer, S.M.; Richie, M.; Durante, M.; Pandite, L.; Goodman, V.; Slamon, D. A randomized and openlabel trial evaluating the addition of pazopanib to lapatinib as firstline therapy in patients with HER2-positive advanced breast cancer. Breast Cancer Res. Tr., 2013, 137(3), 755-766.
137. Schuler, M.; Awada, A.; Harter, P.; Canon, J.L.; Possinger, K.; Schmidt, M.; De Greve, J.; Neven, P.; Dirix, L.; Jonat, W. A phase II trial to assess efficacy and safety of afatinib in extensively pretreated patients with HER2-negative metastatic breast cancer. Breast Cancer Res. Tr., 2012, 134(3), 1149-1159.
138. Roy, V.; Perez, E.A. Beyond trastuzumab: small molecule tyrosine kinase inhibitors in HER-2-positive breast cancer. Oncologist, 2009, 14(11), 1061-1069.
139. Nielsen, D.L.; Kumler, I.; Palshof, J.A.; Andersson, M. Efficacy of HER2-targeted therapy in metastatic breast cancer. Monoclonal antibodies and tyrosine kinase inhibitors. Breast, 2013, 22(1), 1-12.
140. Gostring, L.; Malm, M.; Hoiden-Guthenberg, I.; Frejd, F.Y.; Stahl, S.; Lofblom, J.; Gedda, L. Cellular effects of HER3-specific affibody molecules. PloS One, 2012, 7(6), e40023.
141. Wong, K.K.; Fracasso, P.M.; Bukowski, R.M.; Lynch, T.J.; Munster, P.N.; Shapiro, G.I.; Janne, P.A.; Eder, J.P.; Naughton, M. J.; Ellis, M.J. A phase I study with neratinib (HKI-272), an irreversible pan ErbB receptor tyrosine kinase inhibitor, in patients with solid tumors. Clin. Cancer Res., 2009, 15(7), 2552-2558.
142. Laplante, M.; Sabatini, D.M. mTOR signaling at a glance. J. Cell Sci., 2009, 122(20), 3589-3594.
143. Harvey, R.D.; Lonial, S. PI3 kinase/AKT pathway as a therapeutic target in multiple myeloma. Future Oncol., 2007, 3(6), 639-647.
144. Friedrichs, W.E.; Russell, D.H.; Donzis, E.J.; Middleton, A.K.; Silva, J.M.; Roth, R.A.; Hidalgo, M. Inhibition of mTOR activity restores tamoxifen response in breast cancer cells with aberrant Akt Activity. Clin. Cancer Res., 2004, 10(23), 8059-8067.
145. Lauring, J.; Park, B. H.; Wolff, A. C. The phosphoinositide-3- kinase-Akt-mTOR pathway as a therapeutic target in breast cancer. J. Natil. Compr. Cancer Netw., 2013, 11(6), 670-678.
146. De Marco, C.; Rinaldo, N.; Bruni, P.; Malzoni, C.; Zullo, F.; Fabiani, F.; Losito, S.; Scrima, M.; Marino, F. Z.; Franco, R. Multiple genetic alterations within the PI3K pathway are responsible for AKT activation in patients with ovarian carcinoma. PloS One, 2013, 8(2), e55362.
147. Yardley, D.A. Combining mTOR inhibitors with chemotherapy and other targeted therapies in advanced breast cancer: Rationale, clinical experience, and future directions. Breast Cancer (Auckl), 2013, 7, 7-22.
148. Tinoco, G.; Warsch, S.; Gluck, S.; Avancha, K.; Montero, A.J. Treating breast cancer in the 21st century: Emerging biological therapies. J. Cancer, 2013, 4(2), 117-132.
149. Hennessy, B.T.; Smith, D.L.; Ram, P.T.; Lu, Y.; Mills, G.B. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat. Rev. Drug Discov., 2005, 4(12), 988-1004.
150. Fong, P.C.; Boss, D.S.; Yap, T.A.; Tutt, A.; Wu, P.; Mergui-Roelvink, M.; Mortimer, P.; Swaisland, H.; Lau, A.; O’Connor, M.J. Inhibition of poly (ADP-ribose) polymerase in tumors from BRCA mutation carriers. New Engl. J. Med., 2009, 361(2), 123-134.
151. Krishnakumar, R.; Kraus, W.L. The PARP side of the nucleus: Molecular actions, physiological outcomes, and clinical targets. Mol Cell., 2010, 39(1), 8-24.
152. Amir, E.; Seruga, B.; Serrano, R.; Ocana, A. Targeting DNA repair in breast cancer: A clinical and translational update. Cancer Trea Rev., 2010, 36(7), 557-565.
153. Rojo, F.; Garcia-Parra, J.; Zazo, S.; Tusquets, I.; Ferrer-Lozano, J.; Menendez, S.; Eroles, P.; Chamizo, C.; Servitja, S.; Ramirez-Merino, N. Nuclear PARP-1 protein overexpression is associated with poor overall survival in early breast cancer. Ann. Oncol., 2012, 23(5), 1156-1164.
154. Kummar, S.; Chen, A.; Parchment, R.E.; Kinders, R.J.; Ji, J.; Tomaszewski, J.E.; Doroshow, J.H. Advances in using PARP inhibitors to treat cancer. BMC Med.,2012, 10(1), 25.
155. Singh, S.; Makwana, D.K.; Buckley, T.; Agrawal, A.; Koduru, S. V.; Tiwari, A.K. Clinical Significance of PARP-1 Inhibitors in Cancer Chemotherapy. Trans Clin. Bio., 2013, 1(1), 10-15.
156. Toss, A.; Cortesi, L. Molecular Mechanisms of PARP Inhibitors in BRCA-related Ovarian Cancer. J. Cancer Sci. Ther., 2013, 5, 409-416.
157. Chiarugi, A. A snapshot of chemoresistance to PARP inhibitors. Trends Pharmacol. Sci., 2012, 33(1), 42-48.