Abstract：
:Aromatase inhibitors (AIs) are used for treatment of estrogen receptor α (ER)-positive breast cancer; however, resistance is a major obstacle for optimal outcome. This preclinical study aimed at identifying potential new treatment targets in AI-resistant breast cancer cells. Parental MCF-7 breast cancer cells and four newly established cell lines, resistant to the AIs exemestane or letrozole, were used for a functional kinase inhibitor screen. A library comprising 195 different compounds was tested for preferential growth inhibition of AI-resistant cell lines. Selected targets were validated by analysis of cell growth, cell cycle phase distribution, protein expression, and subcellular localization. We identified 24 compounds, including several inhibitors of Aurora kinases e.g., JNJ-7706621 and barasertib. Protein expression of Aurora kinase A and B was found upregulated in AI-resistant cells compared with MCF-7, and knockdown studies showed that Aurora kinase A was essential for AI-resistant cell growth. In AI-resistant cell lines, the clinically relevant Aurora kinase inhibitors alisertib and danusertib blocked cell cycle progression at the G2/M phase, interfered with chromosome alignment and spindle pole formation, and resulted in preferential growth inhibition compared with parental MCF-7 cells. Even further growth inhibition was obtained when combining the Aurora kinase inhibitors with the antiestrogen fulvestrant. Our study is the first to demonstrate that Aurora kinase A and B may be treatment targets in AI-resistant cells, and our data suggest that therapy targeting both ER and Aurora kinases may be a potent treatment strategy for overcoming AI resistance in breast cancer.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Hole S,Pedersen AM,Lykkesfeldt AE,Yde CWdoi
10.1007/s10549-015-3284-8subject
Has Abstractpub_date
2015-02-01 00:00:00pages
715-26issue
3eissn
0167-6806issn
1573-7217journal_volume
149pub_type
杂志文章abstract：PURPOSE:When combined with anthracyclines, the humanized anti-HER2 monoclonal antibody trastuzumab (Herceptin) provides significant clinical benefit for women with HER2-overexpressing metastatic breast cancer. However, its use is limited by severe cardiotoxicity. To clarify whether myocardial HER2 and HER4 expression i...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1023/b:brea.0000003916.39959.73
更新日期：2003-11-01 00:00:00
abstract：BACKGROUND:Breast cancer is characterized by malignant transformation of epithelial cells, but stromal cells also play an important role in tumorigenesis. While tumor-derived fibroblasts display unique phenotypic properties, it is unclear whether they also represent are a specific subpopulation. MATERIALS AND METHODS:...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-007-9725-2
更新日期：2008-07-01 00:00:00
abstract：:Tumour hypoxia, being widespread in solid tumours, is related to an increased risk of invasion and metastasis as well as to resistance to chemotherapy and radiotherapy. Hypoxia-inducible factor-1alpha (HIF-1alpha) has emerged as the key regulator of the cellular response to hypoxia. In primary breast cancers, HIF-1alp...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-007-9589-5
更新日期：2008-03-01 00:00:00
abstract：:To determine whether recent genome-wide association studies that reported 45 susceptibility loci in European women are also risk factors for breast cancer in Chinese women. We selected and genotyped 40 single nucleotide polymorphisms (SNPs) using the Sequenom iPlex platform in a female Chinese cohort of 2,901 breast c...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-014-3041-4
更新日期：2014-08-01 00:00:00
abstract：PURPOSE:The purpose of this study was to determine the effects of an 8-week high-intensity interval training (HIIT) intervention on vascular endothelial function, measured as brachial artery flow-mediated dilation (baFMD), and vascular wall thickness measured by carotid intima media thickness (cIMT) in breast cancer pa...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章,随机对照试验
doi：10.1007/s10549-019-05332-7
更新日期：2019-09-01 00:00:00
abstract：:Our previous study found cancer detection rates were equivalent for direct radiography compared to screen-film mammography, while rates for computed radiography were significantly lower. This study compares prognostic features of invasive breast cancers by type of mammography. Approved by the University of Toronto Res...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-014-3088-2
更新日期：2014-09-01 00:00:00
abstract：BACKGROUND:Analysis of cytokines and growth factors in human milk offers a noninvasive approach for studying the microenvironment of the postpartum breast, which may better reflect tissue levels than testing blood samples. Given that Black women have a higher incidence of early-onset breast cancers than White women, we...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-018-4907-7
更新日期：2018-11-01 00:00:00
abstract：PURPOSE:Breast cancer brain metastases (BCBM) are becoming an increasingly common diagnosis due to improved systemic control and more routine surveillance imaging. Treatment continues to require a multidisciplinary approach managing systemic and intracranial disease burden. Although, improvements have been made in the ...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章,评审
doi：10.1007/s10549-020-05552-2
更新日期：2020-04-01 00:00:00
abstract：:HER2/neu overexpression leads to poorer prognosis and higher risk of disease reoccurrence in breast cancer patients. The causative factors responsible for increasing HER2/neu expression levels on mammary cells are not known. We investigated whether factors associated with inflammation or metastasis could induce HER2/n...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-012-2191-5
更新日期：2012-09-01 00:00:00
abstract：:The pharmacokinetics of free and different liposomal formulations of hexadecylphosphocholine (HPC) was investigated in tumor-bearing (human mammary tumor MaTu) and tumor-free mice after intravenous and intraperitoneal administration. The levels of HPC were evaluated at different times in serum, normal tissues, and tum...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1023/a:1006224611505
更新日期：1999-11-01 00:00:00
abstract：OBJECTIVE:To measure the association between dietary fiber intake and eleven hormones and peptides in postmenopausal breast cancer survivors. METHODS:Intake of fiber from food and supplements was measured two to three years after breast cancer diagnosis in 493 postmenopausal women from three western states. Concurrent...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-007-9834-y
更新日期：2008-11-01 00:00:00
abstract：:This analysis was conducted to determine whether comorbid medical conditions predict additional breast cancer events and all-cause mortality in women with a history of early stage breast cancer. Women (n = 2,542) participating in a randomized diet trial completed a self-administered questionnaire regarding whether the...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章,多中心研究
doi：10.1007/s10549-010-0732-3
更新日期：2010-08-01 00:00:00
abstract：:Seventy-two patients underwent dye-guided or dye- and gamma probe-guided sentinel lymphadenectomy (SLND) followed by complete axillary lymph node dissection (ALND). The results of imprint cytology, frozen sections, and permanent sections of the sentinel lymph node (SLN) were compared to each other and to the histologi...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1023/a:1006268426526
更新日期：1999-09-01 00:00:00
abstract：:An association between hormone receptors in primary breast cancer and obesity determined prior to mastectomy was investigated in 128 Japanese women. The following criteria for obesity were used: (1) weight greater than or equal to 60 kg (132 lbs), (2) weight kg/height cm-105 greater than or equal to 1.3, (3) weight lb...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/BF01805867
更新日期：1981-01-01 00:00:00
abstract：:Breast reduction is a common surgical procedure performed by plastic and oncoplastic breast surgeons. The authors report on the incidence and management of cancer and atypical hyperplasia in breast reduction specimens from one institution over a 10-year period. All patients who underwent breast reduction surgery at No...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-011-1589-9
更新日期：2011-08-01 00:00:00
abstract：BACKGROUND:Paget's disease of the nipple is a rare form of breast cancer characterised by the presence of intraepidermal tumour cells. It is often associated with ductal carcinoma in situ (DCIS) and/or invasive cancer in the breast parenchyma. We have studied the presentation and symptoms of Paget's disease, local cont...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-007-9783-5
更新日期：2008-09-01 00:00:00
abstract：PURPOSE:To investigate and compare the effects of mobile health (mHealth) and pedometer with conventional exercise program using a brochure on physical function and quality of life (QOL). METHODS:The study was a prospective, quasi-randomized multicenter trial where 356 patients whose cancer treatment had been terminat...
journal_title：Breast cancer research and treatment
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：10.1007/s10549-016-4065-8
更新日期：2017-02-01 00:00:00
abstract：AIMS:Anthracyclines-taxanes containing regimens are widely used for breast cancer treatment both in neoadjuvant-adjuvant setting and in metastatic disease. Recently high-dose chemotherapy (HDC) with autologous stem cell support has been introduced as adjuvant treatment for high-risk primary breast cancer and for select...
journal_title：Breast cancer research and treatment
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1023/a:1006462023110
更新日期：2000-06-01 00:00:00
abstract：PURPOSE:We sought to determine if bioimpedance spectroscopy (BIS) measurements can accurately assess changes in breast cancer-related lymphedema (BCRL) in patients undergoing lymphovenous bypass (LVB). METHODS:Patients undergoing LVB for BCRL refractory to conservative treatment from 1/2015 to 12/2018 were identified ...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章,评审
doi：10.1007/s10549-020-06059-6
更新日期：2021-01-04 00:00:00
abstract：:Cyclin D1 (CCND1), a key cell cycle regulatory protein that governs the cell cycle progression from G1 to S phase, can promote cell proliferation or induce growth arrest and apoptosis. Since the identification of a well-characterized functional polymorphism, G870A in exon 4 of CCND1, several molecular epidemiological ...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章,meta分析
doi：10.1007/s10549-008-0195-y
更新日期：2009-08-01 00:00:00
abstract：:Fresh organically grown pomegranates (Punica granatum L.) of the Wonderful cultivar were processed into three components: fermented juice, aqueous pericarp extract and cold-pressed or supercritical CO2-extracted seed oil. Exposure to additional solvents yielded polyphenol-rich fractions ('polyphenols') from each of th...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1023/a:1014405730585
更新日期：2002-02-01 00:00:00
abstract：:Evidence suggests early events might modify adult breast cancer risk and many adolescents learn of familial and genetic risks for breast cancer. Little is known about how adolescent girls understand and respond to breast cancer risk. Semi-structured interviews with 11-19 year-old girls at high-risk and population-risk...
journal_title：Breast cancer research and treatment
pub_type： 临床试验,杂志文章
doi：10.1007/s10549-012-2254-7
更新日期：2012-12-01 00:00:00
abstract：:The 2008 Physical Activity (PA) Guidelines recommend engaging in at least 2.5 h (10 MET-hours/week) of moderate intensity PA per week (defined as 4 METs) to reduce risk of morbidity and mortality. This analysis was conducted to investigate whether this recommendation can be extended to breast cancer survivors. Data fr...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-011-1770-1
更新日期：2012-01-01 00:00:00
abstract：PURPOSE:Ki-67 has been clinically validated for risk assessment in breast cancer, but the analytical validation and cutpoint-definition remain a challenge. Intraclass correlation coefficients (ICCs) are a statistical parameter for Ki-67 interobserver performance. However, the maximum degree of variance among pathologis...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-018-05112-9
更新日期：2019-08-01 00:00:00
abstract：PURPOSE:Ductal carcinoma in situ (DCIS) is well-known precursor of invasive ductal carcinoma (IDC). Parts of patients show recurrence as DCIS or IDC after local treatment, but there are no established markers predicting relapse. We analyzed changes in miRNA and oncogene expression during DCIS progression/evolution to i...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-019-05192-1
更新日期：2019-07-01 00:00:00
abstract：:There remains a high unmet need for effective treatments for metastatic breast cancer. In recent years there have been many advances in the understanding of biological basis of cancer. Several cellular pathways have been identified that play crucial roles in causing or maintaining the cancer phenotype. Many new agents...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章,评审
doi：10.1007/s10549-008-0268-y
更新日期：2009-07-01 00:00:00
abstract：PURPOSE:Peripheral blood lymphopenia and elevated neutrophil-to-lymphocyte ratio (NLR) have been associated with poor outcomes in various malignancies. However, existing literature has largely focused on baseline parameters. The aim of this study is to assess the impact of radiation therapy (RT) and chemotherapy on abs...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-018-05106-7
更新日期：2019-04-01 00:00:00
abstract：:Axillary management in breast cancer is becoming increasingly conservative. This approach is based on the identification of low axillary burden on sentinel node biopsy (SNB). The modern practice of routine pre-operative axillary ultrasound has meant that patients are 'fast tracked' to axillary node clearance (ANC) in ...
journal_title：Breast cancer research and treatment
pub_type： 社论
doi：10.1007/s10549-017-4313-6
更新日期：2017-09-01 00:00:00
abstract：:Carcinoma of the breast is very rare in childhood, accounting for less than 1% of all childhood malignancies and is especially rare in boys. Delay in diagnosis and treatment in children with breast cancer may occur because surgeons are very reluctant to perform biopsies on the developing breast, since these can cause ...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章,评审
doi：10.1007/s10549-011-1869-4
更新日期：2012-06-01 00:00:00
abstract：PURPOSE:This study aimed to examine the prevalence and trends of breast cancer-related risk factors and characteristics in premenopausal underweight Korean women according to birth year cohort. METHODS:Socioeconomic and breast cancer-related risk factors were investigated in 13,415 premenopausal women using nationwide...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章
doi：10.1007/s10549-018-05091-x
更新日期：2019-04-01 00:00:00
