Hostname: page-component-78c5997874-lj6df Total loading time: 0 Render date: 2024-11-05T05:12:14.540Z Has data issue: false hasContentIssue false

Novel insight into triple-negative breast cancers, the emerging role of angiogenesis, and antiangiogenic therapy

Published online by Cambridge University Press:  07 November 2016

Cornelia Braicu*
Affiliation:
Research Centre for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
Roxana Chiorean
Affiliation:
Department of Dermatology, University of Freiburg, Freiburg, Germany
Alexandru Irimie
Affiliation:
Department of Surgical Oncology and Gynaecological Oncology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania MEDFUTURE-Research Center for Advanced Medicine, University of Medicine and Pharmacy Iuliu-Hatieganu, Cluj-Napoca, Romania Department of Surgery, The Oncology Institute Prof. Dr. Ion Chiricuta, Cluj-Napoca, Romania
Sergiu Chira
Affiliation:
Research Centre for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
Ciprian Tomuleasa
Affiliation:
Research Centre for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
Emilian Neagoe
Affiliation:
Department of Surgical Oncology and Gynaecological Oncology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
Angelo Paradiso
Affiliation:
National Cancer Research Centre, Istituto Tumori G Paolo II, Bari, Italy
Patriciu Achimas-Cadariu
Affiliation:
Department of Surgical Oncology and Gynaecological Oncology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania Department of Surgery, The Oncology Institute Prof. Dr. Ion Chiricuta, Cluj-Napoca, Romania
Vladimir Lazar
Affiliation:
WIN Consortium Villejuif, Paris, France
Ioana Berindan-Neagoe*
Affiliation:
Research Centre for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania Department of Functional Genomics and Experimental Pathology, The Oncology Institute Prof. Dr. Ion Chiricuta, Cluj-Napoca, Romania Department of Experimental Therapeutics, M.D. Anderson Cancer Center, Houston, TX, USA
*
*Corresponding author: Cornelia Braicu and Ioana Berindan-Neagoe, Research Centre for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania. E-mail: [email protected] and [email protected]
*Corresponding author: Cornelia Braicu and Ioana Berindan-Neagoe, Research Centre for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania. E-mail: [email protected] and [email protected]

Abstract

Triple-negative breast cancer (TNBC) is a heterogeneous group of tumours characterised by lack of expression of oestrogen-, progesterone- and human epidermal growth factor receptors. TNBC, which represents approximately 15% of all mammary tumours, has a poor prognosis because of an aggressive behaviour and the lack of specific treatment. Accordingly, TNBC has become a major focus of research into breast cancer and is now classified into several molecular subtypes, each with a different prognosis. Pathological angiogenesis occurs at a late stage in the proliferation of TNBC and is associated with invasion and metastasis; there is an association with metabolic syndrome. Semaphorins are a versatile family of proteins with multiple roles in angiogenesis, tumour growth and metastasis and may represent a clinically useful focus for therapeutic targeting in this type of breast cancer. Another important field of investigation into the control of pathological angiogenesis is related to the expression of noncoding RNA (ncRNA) – these molecules can be considered as a therapeutic target or as a biomarker. Several molecular agents for intervening in the activity of different signalling pathways are being explored in TNBC, but none has so far proved effective in clinical trials and the disease continues to pose a defining challenge for clinical management as well as innovative cancer research.

Type
Review
Copyright
Copyright © Cambridge University Press 2016 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Hergueta-Redondo, M. et al. (2008) “New” molecular taxonomy in breast cancer. Clinical & Translational Oncology 10, 777-785 Google Scholar
2. Yanagawa, M. et al. (2012) Luminal A and luminal B (HER2 negative) subtypes of breast cancer consist of a mixture of tumors with different genotype. BMC Research Notes 5, 376-376 Google Scholar
3. Perou, C.M. et al. (2000) Molecular portraits of human breast tumours. Nature 406, 747-752 Google Scholar
4. Ribelles, N. et al. (2013) Pattern of recurrence of early breast cancer is different according to intrinsic subtype and proliferation index. Breast Cancer Research 15, R98 Google Scholar
5. Peddi, P.F., Ellis, M.J. and Ma, C. (2012) Molecular basis of triple negative breast cancer and implications for therapy. International Journal of Breast Cancer 2012, 217185 Google Scholar
6. Ademuyiwa, F.O., Ellis, M.J. and Ma, C.X. (2013) Neoadjuvant therapy in operable breast cancer: application to triple negative breast cancer. Journal of Oncology 2013, 219869 Google Scholar
7. Liu, N.Q. et al. (2014) Comparative proteome analysis revealing an 11-protein signature for aggressive triple-negative breast cancer. Journal of the National Cancer Institute 106, djt376 Google Scholar
8. Turner, N.C. and Reis-Filho, J.S. (2013) Tackling the diversity of triple-negative breast cancer. Clinical Cancer Research 19, 6380-6388 Google Scholar
10. Brewster, A.M., Chavez-MacGregor, M. and Brown, P. (2014) Epidemiology, biology, and treatment of triple-negative breast cancer in women of African ancestry. The Lancet. Oncology 15, e625-e634 Google Scholar
11. Masuda, H. et al. (2013) Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes. Clinical Cancer Research 19, 5533-5540 Google Scholar
12. Pegram, M.D. et al. (1998) Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. Journal of Clinical Oncology 16, 2659-2671 Google Scholar
13. Carey, L.A. et al. (2007) The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clinical Cancer Research 13, 2329-2334 Google Scholar
14. Hicks, C. et al. (2013) An integrative genomics approach for associating GWAS information with triple-negative breast cancer. Cancer Informatics 12, 1-20 Google Scholar
15. Dent, R.A. et al. (2013) Phase I trial of the oral PARP inhibitor olaparib in combination with paclitaxel for first- or second-line treatment of patients with metastatic triple-negative breast cancer. Breast Cancer Research 15, R88 Google Scholar
16. Minami, C.A., Chung, D.U. and Chang, H.R. (2011) Management options in triple-negative breast cancer. Breast Cancer: Basic and Clinical Research 5, 175-199 Google Scholar
17. Lehmann, B.D. et al. (2011) Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. Journal of Clinical Investigation 121, 2750-2767 Google Scholar
18. Zhang, J. et al. (2015) A phase II trial of biweekly vinorelbine and oxaliplatin in second- or third-line metastatic triple-negative breast cancer. Cancer Biology & Therapy 16, 225-232 Google Scholar
19. Fox, S.B., Generali, D.G. and Harris, A.L. (2007) Breast tumour angiogenesis. Breast Cancer Research 9, 216 Google Scholar
20. Garraway, L.A. and Lander, E.S. (2013) Lessons from the cancer genome. Cell 153, 17-37 Google Scholar
21. Jamdade, V.S. et al. (2015) Therapeutic targets of triple-negative breast cancer: a review. British Journal of Pharmacology 172, 4228-4237 Google Scholar
22. Prat, A. et al. (2013) Molecular characterization of basal-like and non-basal-like triple-negative breast cancer. Oncologist 18, 123-133 Google Scholar
23. Cheang, M.C.U. et al. (2015) Defining breast cancer intrinsic subtypes by quantitative receptor expression. Oncologist 20, 474-482 Google Scholar
24. Chen, X. et al. (2012) TNBCtype: a subtyping tool for triple-negative breast cancer. Cancer Informatics 11, 147-156 Google Scholar
25. Abramson, V.G. et al. (2015) Subtyping of triple-negative breast cancer: implications for therapy. Cancer 121, 8-16 Google Scholar
26. Sabatier, R. et al. (2011) A gene expression signature identifies two prognostic subgroups of basal breast cancer. Breast Cancer Research and Treatment 126, 407-420 Google Scholar
27. Bertucci, F. et al. (2006) Gene expression profiling shows medullary breast cancer is a subgroup of basal breast cancers. Cancer Research 66, 4636-4644 Google Scholar
28. Remo, A. et al. (2015) Systems biology analysis reveals NFAT5 as a novel biomarker and master regulator of inflammatory breast cancer. Journal of Translational Medicine 13, 138 Google Scholar
29. Zhang, H. et al. (2014) Patient-derived xenografts of triple-negative breast cancer reproduce molecular features of patient tumors and respond to mTOR inhibition. Breast Cancer Research 16, R36 Google Scholar
30. Lehmann, B.D., Pietenpol, J.A. and Tan, A.R. (2015) Triple-negative breast cancer: molecular subtypes and new targets for therapy. American Society of Clinical Oncology Educational Book/ASCO. American Society of Clinical Oncology. Meeting, e31-e39Google Scholar
31. Lehmann, B.D. and Pietenpol, J.A. (2014) Identification and use of biomarkers in treatment strategies for triple-negative breast cancer subtypes. Journal of Pathology 232, 142-150 Google Scholar
32. Murakami, M., Elfenbein, A. and Simons, M. (2008) Non-canonical fibroblast growth factor signalling in angiogenesis. Cardiovascular Research 78, 223-231 Google Scholar
33. Jain, R.K. (2003) Molecular regulation of vessel maturation. Nature Medicine 9, 685-693 Google Scholar
34. Papa, A. et al. (2015) Triple-negative breast cancer: investigating potential molecular therapeutic target. Expert Opinion on Therapeutic Targets 19, 55-75 Google Scholar
35. Bender, R.J. and Mac Gabhann, F. (2013) Expression of VEGF and semaphorin genes define subgroups of triple negative breast cancer. PLoS ONE 8, e61788 CrossRefGoogle ScholarPubMed
36. Li, C., et al. (2011) Significance of AEG-1 expression in correlation with, VEGF., microvessel density and clinicopathological characteristics in triple-negative breast cancer. Journal of Surgical Oncology 103, 184-192 Google Scholar
37. Tolaney, S.M., Boucher, Y., Duda, D.G. et al. (2015) Role of vascular density and normalization in response to neoadjuvant bevacizumab and chemotherapy in breast cancer patients. Proceedings of the National Academy of Sciences of the United States of America 112, 14325-14330 Google Scholar
38. Mohammed, R.A., et al. (2011) Lymphatic and blood vessels in basal and triple-negative breast cancers: characteristics and prognostic significance. Modern Pathology 24, 774-785 Google Scholar
39. Hurvitz, S. and Mead, M. (2016) Triple-negative breast cancer: advancements in characterization and treatment approach. Current Opinion in Obstetrics & Gynecology 28, 59-69 Google Scholar
40. Ribeiro-Silva, A., Ribeiro do Vale, F. and Zucoloto, S. (2006) Vascular endothelial growth factor expression in the basal subtype of breast carcinoma. American Journal of Clinical Pathology 125, 512-518 Google Scholar
41. Li, L.Q. et al. (2012) Progranulin expression in breast cancer with different intrinsic subtypes. Pathology, Research and Practice 208, 210-216 Google Scholar
42. Ortiz-Martinez, F., et al. (2015) Osteopontin regulates VEGFA and ICAM-1 mRNA expression in breast carcinoma. American Journal of Clinical Pathology 143, 812-822 Google Scholar
43. Bahnassy, A. et al. (2015) Molecular biomarkers for prediction of response to treatment and survival in triple negative breast cancer patients from Egypt. Experimental and Molecular Pathology 99, 303-311 Google Scholar
44. De Laurentiis, M., et al. (2010) Treatment of triple negative breast cancer (TNBC): current options and future perspectives. Cancer Treatment Reviews 36 (Suppl 3), S80-86 Google Scholar
45. Bahhnassy, A., et al. (2015) Transforming growth factor-beta, insulin-like growth factor I/insulin-like growth factor I receptor and vascular endothelial growth factor-A: prognostic and predictive markers in triple-negative and non-triple-negative breast cancer. Molecular Medicine Reports 12, 851-864 Google Scholar
46. Ryden, L. et al. (2010) Epidermal growth factor receptor and vascular endothelial growth factor receptor 2 are specific biomarkers in triple-negative breast cancer. Results from a controlled randomized trial with long-term follow-up. Breast Cancer Research and Treatment 120, 491-498 Google Scholar
47. Tanaka, T., et al. (2017) Low-dose farnesyltransferase inhibitor suppresses HIF-1α and snail expression in triple-negative breast cancer MDA-MB-231 cells in vitro. Journal of Cellular Physiology 232, 192-201 Google Scholar
48. O'Reilly, E.A., et al. (2015) The fate of chemoresistance in triple negative breast cancer (TNBC). BBA Clinical 3, 257-275 Google Scholar
49. Yehia, L. et al. (2015) Expression of HIF-1alpha and markers of angiogenesis are not significantly different in triple negative breast cancer compared to other breast cancer molecular subtypes: implications for future therapy. PLoS ONE 10, e0129356 Google Scholar
50. van der Groep, P., et al. (2013) HIF-1alpha overexpression in ductal carcinoma in situ of the breast in BRCA1 and BRCA2 mutation carriers. PLoS ONE 8, e56055 Google Scholar
51. van der Groep, P. et al. (2008) High frequency of HIF-1alpha overexpression in BRCA1 related breast cancer. Breast Cancer Research and Treatment 111, 475-480 Google Scholar
52. Wang, X., et al. (2008) Increased expression of osteopontin in patients with triple-negative breast cancer. European Journal of Clinical Investigation 38, 438-446 Google Scholar
53. Ji, H., et al. (2014) TNFR1 mediates TNF-alpha-induced tumour lymphangiogenesis and metastasis by modulating VEGF-C-VEGFR3 signalling. Nature Communications 5, 4944 Google Scholar
54. Qiao, Y. et al. (2016) AP-1 is a key regulator of proinflammatory cytokine TNFalpha-mediated triple-negative breast cancer progression. Journal of Biological Chemistry 291, 5068-5079 Google Scholar
55. Pileczki, V. et al. (2012) TNF-alpha gene knockout in triple negative breast cancer cell line induces apoptosis. International Journal of Molecular Sciences 14, 411-420 Google Scholar
56. Desmarais, J.A. et al. (2008) Spatiotemporal expression pattern of progranulin in embryo implantation and placenta formation suggests a role in cell proliferation, remodeling, and angiogenesis. Reproduction (Cambridge, England) 136, 247-257 Google Scholar
57. Yotsumoto, F., et al. (2013) Molecular hierarchy of heparin-binding EGF-like growth factor-regulated angiogenesis in triple-negative breast cancer. Molecular Cancer Research: MCR 11, 506-517 Google Scholar
58. Saponaro, C., et al. (2013) VEGF, HIF-1alpha expression and MVD as an angiogenic network in familial breast cancer. PLoS ONE 8, e53070 Google Scholar
59. Maric, G. et al. (2013) Glycoprotein non-metastatic b (GPNMB): a metastatic mediator and emerging therapeutic target in cancer. OncoTargets and Therapy 6, 839-852 Google Scholar
60. Karlsson, C., et al. (2010) Genome-wide expression profiling reveals new candidate genes associated with osteoarthritis. Osteoarthritis and Cartilage/OARS, Osteoarthritis Research Society 18, 581-592 Google Scholar
61. Abdelmagid, S.M., et al. (2010) Temporal and spatial expression of osteoactivin during fracture repair. Journal of Cellular Biochemistry 111, 295-309 Google Scholar
62. Rose, A.A., et al. (2010) ADAM10 releases a soluble form of the GPNMB/Osteoactivin extracellular domain with angiogenic properties. PLoS ONE 5, e12093 Google Scholar
63. Duffy, M.J., Crown, J. and Mullooly, M. (2014) ADAM10 and ADAM17: new players in trastuzumab tesistance. Oncotarget 5, 10963-10964 Google Scholar
64. Danza, K., et al. (2014) Combined microRNA and ER expression: a new classifier for familial and sporadic breast cancer patients. Journal of Translational Medicine 12, 319 Google Scholar
65. Danza, K., et al. (2013) Angiogenetic axis angiopoietins/Tie2 and VEGF in familial breast cancer. European Journal of Human Genetics 21, 824-830 Google Scholar
66. Weidner, N. et al. (1991) Tumor angiogenesis and metastasis – correlation in invasive breast carcinoma. New England Journal of Medicine 324, 1-8 Google Scholar
67. Bendinelli, P. et al. (2009) NF-kappaB activation, dependent on acetylation/deacetylation, contributes to HIF-1 activity and migration of bone metastatic breast carcinoma cells. Molecular Cancer Research 7, 1328-1341 Google Scholar
68. Chen, X., et al. (2013) Angiotensin II type 1 receptor antagonists inhibit cell proliferation and angiogenesis in breast cancer. Cancer Letters 328, 318-324 Google Scholar
69. Brand, T.M. et al. (2013) Nuclear EGFR as a molecular target in cancer. Radiotherapy and Oncology 108, 370-377 Google Scholar
70. Mukhopadhyay, P., et al. (2013) MUC4 overexpression augments cell migration and metastasis through EGFR family proteins in triple negative breast cancer cells. PLoS ONE 8, e54455 Google Scholar
71. Shapira, I. et al. (2013) P53 mutations in triple negative breast cancer upregulate endosomal recycling of epidermal growth factor receptor (EGFR) increasing its oncogenic potency. Critical Reviews in Oncology/Hematology 88, 284-292 Google Scholar
72. Gabrovska, P.N. et al. (2011) Semaphorin-plexin signalling genes associated with human breast tumourigenesis. Gene 489, 63-69 Google Scholar
73. Toyofuku, T., et al. (2007) Semaphorin-4A, an activator for T-cell-mediated immunity, suppresses angiogenesis via Plexin-D1. EMBO Journal 26, 1373-1384 Google Scholar
74. Guttmann-Raviv, N. et al. (2007) Semaphorin-3A and semaphorin-3F work together to repel endothelial cells and to inhibit their survival by induction of apoptosis. Journal of Biological Chemistry 282, 26294-26305 Google Scholar
75. Bender, R.J. and Mac Gabhann, F. (2015) Dysregulation of the vascular endothelial growth factor and semaphorin ligand-receptor families in prostate cancer metastasis. BMC Systems Biology 9, 55 Google Scholar
76. Basile, J.R., Afkhami, T. and Gutkind, J.S. (2005) Semaphorin 4D/plexin-B1 induces endothelial cell migration through the activation of PYK2, Src, and the phosphatidylinositol 3-kinase-Akt pathway. Molecular and Cellular Biology 25, 6889-6898 Google Scholar
77. Mumblat, Y. et al. (2015) Full-length semaphorin-3C is an inhibitor of tumor lymphangiogenesis and metastasis. Cancer Research 75, 2177-2186 Google Scholar
78. Goel, H.L., et al. (2013) GLI1 regulates a novel neuropilin-2/alpha6beta1 integrin based autocrine pathway that contributes to breast cancer initiation. EMBO Molecular Medicine 5, 488-508 Google Scholar
79. Ellis, L.M. (2006) The role of neuropilins in cancer. Molecular Cancer Therapeutics 5, 1099-1107 Google Scholar
80. Mishra, R., et al. (2015) Semaphorin 3A upregulates FOXO 3a-dependent MelCAM expression leading to attenuation of breast tumor growth and angiogenesis. Oncogene 34, 1584-1595 CrossRefGoogle ScholarPubMed
81. Shen, W.W., et al. (2015) Breast cancer cells promote osteoblastic differentiation via Sema 3A signaling pathway in vitro. International Journal of Clinical and Experimental Pathology 8, 1584-1593 Google Scholar
82. Cole-Healy, Z. et al. (2015) The relationship between semaphorin 3C and microvessel density in the progression of breast and oral neoplasia. Experimental and Molecular Pathology 99, 19-24 Google Scholar
83. Chen, D. et al. (2015) SEMA6D expression and patient survival in breast invasive carcinoma. International Journal of Breast Cancer 2015, 539721 Google Scholar
84. Ju, R.J., et al. (2014) Liposomes, modified with PTD(HIV-1) peptide, containing epirubicin and celecoxib, to target vasculogenic mimicry channels in invasive breast cancer. Biomaterials 35, 7610-7621 Google Scholar
85. Liu, T.J., et al. (2013) CD133+ cells with cancer stem cell characteristics associates with vasculogenic mimicry in triple-negative breast cancer. Oncogene 32, 544-553 Google Scholar
86. Guo, P., et al. (2014) ICAM-1 as a molecular target for triple negative breast cancer. Proceedings of the National Academy of Sciences of the United States of America 111, 14710-14715 Google Scholar
87. Guo, P. et al. (2016) ICAM-1-targeted, Lcn2 siRNA-encapsulating liposomes are potent anti-angiogenic agents for triple negative breast cancer. Theranostics 6, 1-13 Google Scholar
88. Chai, D.M. et al. (2013) Vasculogenic mimicry and aberrant expression of HIF-lalpha/E-cad are associated with worse prognosis of esophageal squamous cell carcinoma. Journal of Huazhong University of Science and Technology. Medical Sciences 33, 385-391 Google Scholar
89. Nieto, Y., et al. (2007) Prognostic analysis of tumour angiogenesis, determined by microvessel density and expression of vascular endothelial growth factor, in high-risk primary breast cancer patients treated with high-dose chemotherapy. British Journal of Cancer 97, 391-397 Google Scholar
90. Kraby, M.R. et al. (2015) Microvascular proliferation in luminal A and basal-like breast cancer subtypes. Journal of Clinical Pathology 68, 891-897 Google Scholar
91. Rubovszky, G. et al. (2012) Significance of histomorphology of early triple-negative breast cancer. Pathology Oncology Research: POR 18, 823-831 Google Scholar
92. Serguienko, A., et al. (2015) Metabolic reprogramming of metastatic breast cancer and melanoma by let-7a microRNA. Oncotarget 6, 2451-2465 Google Scholar
93. Davis, A.A. and Kaklamani, V.G. (2012) Metabolic syndrome and triple-negative breast cancer: a new paradigm. International Journal of Breast Cancer 2012, 809291 Google Scholar
94. Jarde, T. et al. (2011) Molecular mechanisms of leptin and adiponectin in breast cancer. European Journal of Cancer 47, 33-43 Google Scholar
95. Jin, L., et al. (2014) The metastatic potential of triple-negative breast cancer is decreased via caloric restriction-mediated reduction of the miR-17~92 cluster. Breast Cancer Research and Treatment 146, 41-50 CrossRefGoogle ScholarPubMed
96. Maiti, B. et al. (2010) The association of metabolic syndrome with triple-negative breast cancer. Breast Cancer Research and Treatment 121, 479-483 Google Scholar
97. Davison, Z. et al. (2011) Insulin-like growth factor-dependent proliferation and survival of triple-negative breast cancer cells: implications for therapy. Neoplasia 13, 504-515 Google Scholar
98. Bisso, A., et al. (2013) Oncogenic miR-181a/b affect the DNA damage response in aggressive breast cancer. Cell Cycle 12, 1679-1687 Google Scholar
99. Xu, Q., et al. (2015) Regulatory circuit of PKM2/NF-kappaB/miR-148a/152-modulated tumor angiogenesis and cancer progression. Oncogene 34, 5482-5493 Google Scholar
100. Moschos, S., Chan, J.L. and Mantzoros, C.S. (2002) Leptin and reproduction: a review. Fertility and Sterility 77, 433-444 Google Scholar
101. Bluher, S. and Mantzoros, C.S. (2009) Leptin in humans: lessons from translational research. The American Journal of Clinical Nutrition 89, 991s-997s Google Scholar
102. Munzberg, H. et al. (2005) Leptin receptor action and mechanisms of leptin resistance. Cellular and Molecular Life Sciences 62, 642-652 Google Scholar
103. Tessitore, L., et al. (2000) Leptin expression in colorectal and breast cancer patients. International Journal of Molecular Medicine 5, 421-426 Google Scholar
104. Korner, A., et al. (2007) Total and high-molecular-weight adiponectin in breast cancer: in vitro and in vivo studies. Journal of Clinical Endocrinology and Metabolism 92, 1041-1048 Google Scholar
105. Miyoshi, Y., et al. (2003) Association of serum adiponectin levels with breast cancer risk. Clinical Cancer Research 9, 5699-5704 Google Scholar
106. Chen, D.C., et al. (2006) Serum adiponectin and leptin levels in Taiwanese breast cancer patients. Cancer Letters 237, 109-114 Google Scholar
107. Kaaks, R., et al. (2000) Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women. Journal of the National Cancer Institute 92, 1592-1600 Google Scholar
108. Ouchi, N., Shibata, R. and Walsh, K. (2005) AMP-activated protein kinase signaling stimulates VEGF expression and angiogenesis in skeletal muscle. Circulation Research 96, 838-846 Google Scholar
109. Wang, Y., et al. (2005) Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerization-dependent manner. Journal of Biological Chemistry 280, 18341-18347 Google Scholar
110. Le Du, F., et al. (2015) Is the future of personalized therapy in triple-negative breast cancer based on molecular subtype? Oncotarget 6, 12890-12908 Google Scholar
111. Catana, C.S., Calin, G.A. and Berindan-Neagoe, I. (2015) Inflamma-miRs in aging and breast cancer: are they reliable players? Frontiers in Medicine 2, 85 Google Scholar
112. Berindan-Neagoe, I. and Calin, G.A. (2014) Molecular pathways: microRNAs, cancer cells, and microenvironment. Clinical Cancer Research 20, 6247-6253 Google Scholar
113. Braicu, C. et al. (2014) NCRNA combined therapy as future treatment option for cancer. Current Pharmaceutical Design 20, 6565-6574 Google Scholar
114. Chang, C.H., et al. (2014) The prognostic significance of RUNX2 and miR-10a/10b and their inter-relationship in breast cancer. Journal of Translational Medicine 12, 257 Google Scholar
115. Toyama, T., et al. (2012) High expression of microRNA-210 is an independent factor indicating a poor prognosis in Japanese triple-negative breast cancer patients. Japanese Journal of Clinical Oncology 42, 256-263 Google Scholar
116. Eades, G. et al. (2015) lincRNA-RoR and miR-145 regulate invasion in triple-negative breast cancer via targeting ARF6. Molecular Cancer Research 13, 330-338 Google Scholar
117. Liu, Y.R. et al. (2016) Comprehensive transcriptome profiling reveals multigene signatures in triple-negative breast cancer. Clinical Cancer Research 22, 1653-1662 Google Scholar
118. Jiang, Y.Z., et al. (2016) Transcriptome analysis of triple-negative breast cancer reveals an integrated mRNA-lncRNA signature with predictive and prognostic value. Cancer Research 76, 2105-2114 Google Scholar
119. Lv, M., et al. (2016) LncRNAs as new biomarkers to differentiate triple negative breast cancer from non-triple negative breast cancer. Oncotarget 7, 13047-13059 Google Scholar
120. Yan, L., et al. (2015) Regulation of tumor cell migration and invasion by the H19/let-7 axis is antagonized by metformin-induced DNA methylation. Oncogene 34, 3076-3084 Google Scholar
121. Lee, S., et al. (2015) Suppression of miR-181a attenuates H(2)O(2)-induced death of mesenchymal stem cells by maintaining hexokinase II expression. Biological Research 48, 45 Google Scholar
122. Lin, A., et al. (2016) The LINK-A lncRNA activates normoxic HIF1alpha signalling in triple-negative breast cancer. Nature Cell Biology 18, 213-224 Google Scholar
123. Augoff, K. et al. (2012) miR-31 and its host gene lncRNA LOC554202 are regulated by promoter hypermethylation in triple-negative breast cancer. Molecular Cancer 11, 5 Google Scholar
124. Antolin, S., et al. (2015) Circulating miR-200c and miR-141 and outcomes in patients with breast cancer. BMC Cancer 15, 297 Google Scholar
125. Yu, Z., et al. (2014) miR-17/20 sensitization of breast cancer cells to chemotherapy-induced apoptosis requires Akt1. Oncotarget 5, 1083-1090 Google Scholar
126. Fang, Y.X. and Gao, W.Q. (2014) Roles of microRNAs during prostatic tumorigenesis and tumor progression. Oncogene 33, 135-147 Google Scholar
127. Abedi, N. et al. (2015) miR-141 as potential suppressor of β-catenin in breast cancer. Tumour Biology 36, 9895-9901 Google Scholar
128. Kim, S., et al. (2015) Bioinformatic and metabolomic analysis reveals miR-155 regulates thiamine level in breast cancer. Cancer Letters 357, 488-497 Google Scholar
129. Nassirpour, R. et al. (2013) miR-221 promotes tumorigenesis in human triple negative breast cancer cells. PLoS ONE 8, e62170 Google Scholar
130. Tseng, L.M. et al. (2012) CIP2A is a target of bortezomib in human triple negative breast cancer cells. Breast Cancer Research 14, R68 Google Scholar
131. Berindan-Neagoe, I., Braicu, C. and Irimie, A. (2012) Combining the chemotherapeutic effects of epigallocatechin 3-gallate with siRNA-mediated p53 knock-down results in synergic pro-apoptotic effects. International Journal of Nanomedicine 7, 6035-6047 Google Scholar
132. Bayraktar, S. and Gluck, S. (2013) Molecularly targeted therapies for metastatic triple-negative breast cancer. Breast Cancer Research and Treatment 138, 21-35 Google Scholar
133. Miller, K., et al. (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. New England Journal of Medicine 357, 2666-2676 Google Scholar
134. Cameron, D., et al. (2013) Adjuvant bevacizumab-containing therapy in triple-negative breast cancer (BEATRICE): primary results of a randomised, phase 3 trial. The Lancet. Oncology 14, 933-942 Google Scholar
135. von Minckwitz, G., et al. (2012) Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. New England Journal of Medicine 366, 299-309 Google Scholar
136. Spanheimer, P.M., et al. (2015) Receptor tyrosine kinase expression predicts response to sunitinib in breast cancer. Annals of Surgical Oncology 22, 4287-4294 Google Scholar
137. Luu, T., et al. (2014) Phase I/II trial of vinorelbine and sorafenib in metastatic breast cancer. Clinical Breast Cancer 14, 94-100 Google Scholar
138. Baselga, J., et al. (2012) Sorafenib in combination with capecitabine: an oral regimen for patients with HER2-negative locally advanced or metastatic breast cancer. Journal of Clinical Oncology 30, 1484-1491 Google Scholar
139. LoRusso, P.M., et al. (2014) Icrucumab, a fully human monoclonal antibody against the vascular endothelial growth factor receptor-1, in the treatment of patients with advanced solid malignancies: a Phase 1 study. Investigational New Drugs 32, 303-311 Google Scholar
140. Chougule, M.B. et al. (2011) Antitumor activity of Noscapine in combination with Doxorubicin in triple negative breast cancer. PLoS ONE 6, e17733 Google Scholar
141. Pasquier, E., et al. (2011) Propranolol potentiates the anti-angiogenic effects and anti-tumor efficacy of chemotherapy agents: implication in breast cancer treatment. Oncotarget 2, 797-809 Google Scholar
142. Witters, L., et al. (2008) Synergistic inhibition with a dual epidermal growth factor receptor/HER-2/neu tyrosine kinase inhibitor and a disintegrin and metalloprotease inhibitor. Cancer Research 68, 7083-7089 Google Scholar
143. Otvos, L. Jr, et al. (2011) Efficacy of a leptin receptor antagonist peptide in a mouse model of triple-negative breast cancer. European Journal of Cancer 47, 1578-1584 Google Scholar
144. Crown, J., O'Shaughnessy, J. and Gullo, G. (2012) Emerging targeted therapies in triple-negative breast cancer. Annals of Oncology 23 (Suppl 6), vi56-vi65 Google Scholar
145. Hein, A., et al. (2015) Genetic variants in VEGF pathway genes in neoadjuvant breast cancer patients receiving bevacizumab: results from the randomized phase III GeparQuinto study. International Journal of Cancer 137, 2981-2988 Google Scholar
146. Williams, C.B. et al. (2015) Perspectives on epidermal growth factor receptor regulation in triple-negative breast cancer: ligand-mediated mechanisms of receptor regulation and potential for clinical targeting. Advances in Cancer Research 127, 253-281 Google Scholar
147. Rosca, E.V., et al. (2014) A biomimetic collagen derived peptide exhibits anti-angiogenic activity in triple negative breast cancer. PLoS ONE 9, e111901 Google Scholar
148. Ham, S.L., et al. (2015) Phytochemicals potently inhibit migration of metastatic breast cancer cells. Integrative Biology: Quantitative Biosciences from Nano to Macro 7, 792-800 Google Scholar
149. Wu, J., et al. (2011) Caffeic acid phenethyl ester (CAPE), derived from a honeybee product propolis, exhibits a diversity of anti-tumor effects in pre-clinical models of human breast cancer. Cancer Letters 308, 43-53 Google Scholar
150. Ferreira, L.C., et al. (2015) Effect of curcumin on pro-angiogenic factors in the xenograft model of breast cancer. Anti-Cancer Agents in Medicinal Chemistry 15, 1285-1296 Google Scholar
151. Lee, H.J., et al. (2011) Oral administration of penta-O-galloyl-beta-D-glucose suppresses triple-negative breast cancer xenograft growth and metastasis in strong association with JAK1-STAT3 inhibition. Carcinogenesis 32, 804-811 Google Scholar
152. Braicu, C. et al. (2013) Epigallocatechin-3-Gallate (EGCG) inhibits cell proliferation and migratory behaviour of triple negative breast cancer cells. Journal of Nanoscience and Nanotechnology 13, 632-637 Google Scholar