Molecular Mechanisms and Emerging Therapeutic Targets of Triple-Negative Breast Cancer Metastasis

被引:130
作者
Neophytou, Christiana [1 ]
Boutsikos, Panagiotis [2 ]
Papageorgis, Panagiotis [2 ]
机构
[1] Univ Cyprus, Sch Pure & Appl Sci, Dept Biol Sci, Nicosia, Cyprus
[2] European Univ Cyprus, Dept Life Sci, Nicosia, Cyprus
关键词
triple-negative breast cancer; metastasis; targeted therapy; tumor microenvironment; dormancy; EPITHELIAL-MESENCHYMAL TRANSITION; BONE METASTASIS; LUNG METASTASIS; TUMOR-GROWTH; MASTER REGULATOR; CELL-MIGRATION; UP-REGULATION; STEM-CELLS; SUPPRESSION; INHIBITION;
D O I
10.3389/fonc.2018.00031
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Breast cancer represents a highly heterogeneous disease comprised by several subtypes with distinct histological features, underlying molecular etiology and clinical behaviors. It is widely accepted that triple-negative breast cancer (TNBC) is one of the most aggressive subtypes, often associated with poor patient outcome due to the development of metastases in secondary organs, such as the lungs, brain, and bone. The molecular complexity of the metastatic process in combination with the lack of effective targeted therapies for TNBC metastasis have fostered significant research efforts during the past few years to identify molecular "drivers" of this lethal cascade. In this review, the most current and important findings on TNBC metastasis, as well as its closely associated basal-like subtype, including metastasis-promoting or suppressor genes and aberrantly regulated signaling pathways at specific stages of the metastatic cascade are being discussed. Finally, the most promising therapeutic approaches and novel strategies emerging from these molecular targets that could potentially be clinically applied in the near future are being highlighted.
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页数:13
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共 136 条
[1]  
Abe O, 2005, LANCET, V366, P2087, DOI 10.1016/s0140-6736(05)66544-0
[2]   A CXCL1 Paracrine Network Links Cancer Chemoresistance and Metastasis [J].
Acharyya, Swarnali ;
Oskarsson, Thordur ;
Vanharanta, Sakari ;
Malladi, Srinivas ;
Kim, Juliet ;
Morris, Patrick G. ;
Manova-Todorova, Katia ;
Leversha, Margaret ;
Hogg, Nancy ;
Seshan, Venkatraman E. ;
Norton, Larry ;
Brogi, Edi ;
Massague, Joan .
CELL, 2012, 150 (01) :165-178
[3]   A Mutant-p53/Smad Complex Opposes p63 to Empower TGFβ-Induced Metastasis [J].
Adorno, Maddalena ;
Cordenonsi, Michelangelo ;
Montagner, Marco ;
Dupont, Sirio ;
Wong, Christine ;
Hann, Byron ;
Solari, Aldo ;
Bobisse, Sara ;
Rondina, Maria Beatrice ;
Guzzardo, Vincenza ;
Parenti, Anna R. ;
Rosato, Antonio ;
Bicciato, Silvio ;
Balmain, Allan ;
Piccolo, Stefano .
CELL, 2009, 137 (01) :87-98
[4]   Fascin Is a Key Regulator of Breast Cancer Invasion That Acts via the Modification of Metastasis-Associated Molecules [J].
Al-Alwan, Monther ;
Olabi, Safiah ;
Ghebeh, Hazem ;
Barhoush, Eman ;
Tulbah, Asma ;
Al-Tweigeri, Taher ;
Ajarim, Dahish ;
Adra, Chaker .
PLOS ONE, 2011, 6 (11)
[5]   Biology, Metastatic Patterns, and Treatment of Patients with Triple-Negative Breast Cancer [J].
Anders, Carey K. ;
Carey, Lisa A. .
CLINICAL BREAST CANCER, 2009, 9 :S73-S81
[6]   Triple negative breast cancer initiating cell subsets differ in functional and molecular characteristics and in γ-secretase inhibitor drug responses [J].
Azzam, Diana J. ;
Zhao, Dekuang ;
Sun, Jun ;
Minn, Andy J. ;
Ranganathan, Prathibha ;
Drews-Elger, Katherine ;
Han, Xiaoqing ;
Picon-Ruiz, Manuel ;
Gilbert, Candace A. ;
Wander, Seth A. ;
Capobianco, Anthony J. ;
El-Ashry, Dorraya ;
Slingerland, Joyce M. .
EMBO MOLECULAR MEDICINE, 2013, 5 (10) :1502-1522
[7]   Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease [J].
Bianchini, Giampaolo ;
Balko, Justin M. ;
Mayer, Ingrid A. ;
Sanders, Melinda E. ;
Gianni, Luca .
NATURE REVIEWS CLINICAL ONCOLOGY, 2016, 13 (11) :674-690
[8]   Myoferlin regulates cellular lipid metabolism and promotes metastases in triple-negative breast cancer [J].
Blomme, A. ;
Costanza, B. ;
de Tullio, P. ;
Thiry, M. ;
Van Simaeys, G. ;
Boutry, S. ;
Doumont, G. ;
Di Valentin, E. ;
Hirano, T. ;
Yokobori, T. ;
Gofflot, S. ;
Peulen, O. ;
Bellahcene, A. ;
Sherer, F. ;
Le Goff, C. ;
Cavalier, E. ;
Mouithys-Mickalad, A. ;
Jouret, F. ;
Cusumano, P. G. ;
Lifrange, E. ;
Muller, R. N. ;
Goldman, S. ;
Delvenne, P. ;
De Pauw, E. ;
Nishiyama, M. ;
Castronovo, V. ;
Turtoi, A. .
ONCOGENE, 2017, 36 (15) :2116-2130
[9]   Genes that mediate breast cancer metastasis to the brain [J].
Bos, Paula D. ;
Zhang, Xiang H. -F. ;
Nadal, Cristina ;
Shu, Weiping ;
Gomis, Roger R. ;
Nguyen, Don X. ;
Minn, Andy J. ;
van de Vijver, Marc J. ;
Gerald, William L. ;
Foekens, John A. ;
Massague, Joan .
NATURE, 2009, 459 (7249) :1005-U137
[10]   Triple-negative breast cancer: Molecular features, pathogenesis, treatment and current lines of research [J].
Bosch, Ana ;
Eroles, Pilar ;
Zaragoza, Rosa ;
Vina, Juan R. ;
Lluch, Ana .
CANCER TREATMENT REVIEWS, 2010, 36 (03) :206-215