Abstract:
:With current techniques, it remains a challenge to assess coregulator binding of nuclear receptors, for example, the estrogen receptor alpha (ERα). ERα is critical in many breast tumors and is inhibited by antiestrogens such as tamoxifen in cancer therapy. ERα is also modified by acetylation and phosphorylation that affect responses to the antiestrogens as well as interactions with coregulators. Phosphorylation of ERα at Ser305 is one of the mechanisms causing tamoxifen resistance. Detection of resistance in patient samples would greatly facilitate clinical decisions on treatment, in which such patients would receive other treatments such as aromatase inhibitors or fulvestrant. Here we describe a coregulator peptide array that can be used for high-throughput analysis of full-length estrogen receptor binding. The peptide chip can detect ERα binding in cell and tumor lysates. We show that ERα phosphorylated at Ser305 associates stronger to various coregulator peptides on the chip. This implies that ERαSer305 phosphorylation increases estrogen receptor function. As this is also detected in a breast tumor sample of a tamoxifen-insensitive patient, the peptide array, as described here, may be applicable to detect tamoxifen resistance in breast tumor samples at an early stage of disease and contribute to personalized medicine.
journal_name
Mol Cancer Therjournal_title
Molecular cancer therapeuticsauthors
Houtman R,de Leeuw R,Rondaij M,Melchers D,Verwoerd D,Ruijtenbeek R,Martens JW,Neefjes J,Michalides Rdoi
10.1158/1535-7163.MCT-11-0855subject
Has Abstractpub_date
2012-04-01 00:00:00pages
805-16issue
4eissn
1535-7163issn
1538-8514pii
1535-7163.MCT-11-0855journal_volume
11pub_type
杂志文章abstract::Invasive ductal carcinomas (IDC) of the breast are associated with altered expression of hormone receptors (HR), amplification or overexpression of HER2, or a triple-negative phenotype. The most aggressive cases of IDC are characterized by a high proliferation rate, a great propensity to metastasize, and their ability...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-14-0945
更新日期:2015-06-01 00:00:00
abstract::Upregulation of HER2 is a hallmark of 20% to 30% of invasive breast cancers, rendering this receptor an attractive target for cancer therapy. Although HER2-targeting agents have provided substantial clinical benefit as cancer therapeutics, there is a need for the development of new agents aiming at circumventing anti-...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-14-0046-T
更新日期:2014-08-01 00:00:00
abstract::Angiogenesis is required for tumor growth and metastasis, and targeting angiogenesis is a novel anticancer strategy. However, cancer development is a complex multistep process, and single antiangiogenic agents have limited therapeutic efficacy. Here, we report a triple fusion protein, namely CTT peptide-endostatin mim...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-14-0266
更新日期:2014-11-01 00:00:00
abstract::The present studies have determined whether interactions between the cyclin-dependent kinase inhibitor flavopiridol and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA; vorinostat; Zolinza) occur in breast cancer cells. MDA-MB-231 and MCF7 cells were treated with flavopiridol (25-100 nmol/L) an...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-07-0561
更新日期:2007-12-01 00:00:00
abstract::Squamous cell carcinoma (SCC) is one of the most common human cancers worldwide. Recent studies show that regulatory T cells (Treg) have a critical role in the modulation of an antitumor immune response, and consequently the SCC development. Because the accumulation of Tregs at the tumor site is, in part, due to selec...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-17-0341
更新日期:2017-12-01 00:00:00
abstract::Resistance to antiandrogen drugs, like MDV3100, occurs in patients with castration-resistant prostate cancer (CRPC). Thus, preventing or treating antiandrogen resistance is a major clinical challenge. We identified a novel antiandrogen, Compound 30, and compared its efficacy with MDV3100. We found that Compound 30 inh...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-12-0798
更新日期:2013-05-01 00:00:00
abstract::The cytotoxicity of 5-aza-2'-deoxycytidine (DAC) has been linked to demethylation of the INK4a/ARF tumor suppressor gene locus in various cell systems, but the causality of this association remains unproven. To test this assumption, we have examined the effects of DAC in two human cancer cell lines of differing INK4a/...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-08-0926
更新日期:2009-04-01 00:00:00
abstract::Clinical decision making for human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is predominantly guided by disease stage and anatomic location, with few validated biomarkers. The epidermal growth factor receptor (EGFR) is an important therapeutic target, but its value in guiding therapeu...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-16-0243
更新日期:2016-10-01 00:00:00
abstract::Expression of fatty acid synthase (FASN), the key enzyme in de novo synthesis of long-chain fatty acids, is normally low but increases in cancer. Consequently, FASN is a novel target for cancer therapy. However, because FASN inhibitors can lead to tumor stasis rather than shrinkage, noninvasive methods for assessing F...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-08-0015
更新日期:2008-08-01 00:00:00
abstract::Tumor glycans constitute attractive targets for therapeutic antibodies. The sialylated glycocalyx plays a prominent role in cancer progression and immune evasion. Here, we describe the characterization of the mAb, FG129, which targets tumor-associated sialylated glycan, and demonstrate its potential for multimodal can...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-19-0221
更新日期:2020-03-01 00:00:00
abstract::ErbB2 tyrosine kinase inhibitors (TKI) block tyrosine autophosphorylation and activation of the full-length transmembrane ErbB2 receptor (p185(ErbB2)). In addition to p185(ErbB2), truncated forms of ErbB2 exist in breast cancer cell lines and clinical tumors. The contribution of these truncated forms, specifically tho...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-10-0991
更新日期:2011-08-01 00:00:00
abstract::Endocrine therapy has been highly effective for the treatment of estrogen receptor-positive breast cancer, but endocrine resistance develops in a significant proportion of patients. In an effort to develop novel therapeutic strategies for the treatment of endocrine-resistant breast cancer, we have evaluated a potent a...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-16-0028
更新日期:2016-12-01 00:00:00
abstract::The oncogenic beta-catenin/T-cell factor (TCF) signal is a common trigger inducing expressions of various cancer-related genes and is activated in various types of human malignancy. The aim of this study was to create an effective double-stranded DNA decoy that would interfere with endogenous TCF hyperactivity in tumo...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-05-0388
更新日期:2006-04-01 00:00:00
abstract::Most patients with late-stage high-grade serous ovarian cancer (HGSOC) initially respond to chemotherapy but inevitably relapse and develop resistance, highlighting the need for novel therapies to improve patient outcomes. The MEK/ERK pathway is activated in a large subset of HGSOC, making it an attractive therapeutic...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-18-0413
更新日期:2019-03-01 00:00:00
abstract::D,L-Sulforaphane (SFN), a synthetic analogue of cruciferous vegetable-derived L-isomer, inhibits the growth of human prostate cancer cells in culture and in vivo and retards cancer development in a transgenic mouse model of prostate cancer. We now show that SFN treatment causes transcriptional repression of androgen r...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-09-0104
更新日期:2009-07-01 00:00:00
abstract::To determine the efficacy of a novel and safer (for gastrointestinal tract) aspirin (aspirin-PC) in preclinical models of ovarian cancer, in vitro dose-response studies were performed to compare the growth-inhibitory effect of aspirin-PC versus aspirin on three human (A2780, SKOV3ip1, and HeyA8) and a mouse (ID8) ovar...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-16-0074
更新日期:2016-12-01 00:00:00
abstract::COX-2 is upregulated in pancreatic ductal adenocarcinomas (PDAC). However, how COX-2 promotes PDAC development is unclear. While previous studies have evaluated the efficacy of COX-2 inhibition via the use of nonsteroidal anti-inflammatory drugs (NSAID) or the COX-2 inhibitor celecoxib in PDAC models, none have addres...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-12-0342
更新日期:2012-10-01 00:00:00
abstract::The androgen receptor (AR) is a key driver and therapeutic target in androgen-sensitive prostate cancer, castration-resistant prostate cancer (CRPC), and CRPC resistant to abiraterone and enzalutamide, two second-generation inhibitors of AR signaling. Because current AR inhibitors target a functioning C-terminal ligan...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-18-0432
更新日期:2019-01-01 00:00:00
abstract::Molecular characterization of radical prostatectomy specimens after systemic therapy may identify a gene expression profile for resistance to therapy. This study assessed tumor cells from patients with prostate cancer participating in a phase II neoadjuvant docetaxel and androgen deprivation trial to identify mediator...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-13-0775
更新日期:2014-05-01 00:00:00
abstract::Constitutively activated STAT3 and STAT5 are expressed in a wide variety of human malignancies including solid and hematopoietic cancers and often correlate with a poor prognosis and resistance to multiple therapies. Given the well established role of STAT3 in tumorigenesis, inhibition of Janus-activated kinase 2 (JAK...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-11-0951
更新日期:2012-04-01 00:00:00
abstract::Tumor-specific tissue-penetrating peptides deliver drugs into extravascular tumor tissue by increasing tumor vascular permeability through interaction with neuropilin (NRP). Here, we report that a prototypic tumor-penetrating peptide iRGD (amino acid sequence: CRGDKGPDC) potently inhibits spontaneous metastasis in mic...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-14-0366
更新日期:2015-01-01 00:00:00
abstract::Involuntary weight loss, a part of the cachexia syndrome, is a debilitating comorbidity of cancer and currently has no treatment options. Results from a recent clinical trial at our institution showed that biliary tract cancer patients treated with a MEK inhibitor exhibited poor tumor responses but surprisingly gained...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-16-0337
更新日期:2017-02-01 00:00:00
abstract::Tumor-associated urokinase plasminogen activator (uPA) is a critical marker of invasion and metastasis, has strong prognostic relevance, and is thus a potential therapeutic target. Experimental data published to date has established the proof-of-principle of uPA targeting by (213)Bi-labeled plasminogen activator inhib...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-06-0264
更新日期:2007-01-01 00:00:00
abstract::The development of new drugs against cancer requires established cell lines. They are needed for in vitro studies to identify candidate drugs and in xenograft models to measure drug efficacy in vivo. Specific criteria need to be fulfilled by cell lines used in the evaluation of potential novel therapeutic agents. It i...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:
更新日期:2003-07-01 00:00:00
abstract::Antiangiogenic therapies targeting VEGFA have been commonly used in clinics to treat cancers over the past decade. However, their clinical efficacy has been limited, with drawbacks including acquisition of resistance and activation of compensatory pathways resulting from elevated circulating VEGFB and placental growth...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-14-0968-T
更新日期:2015-02-01 00:00:00
abstract::G-protein-coupled receptors (GPCR) activate the epidermal growth factor receptor (EGFR) and mediate EGFR-independent signaling pathways to promote the growth of a variety of cancers, including head and neck squamous cell carcinoma (HNSCC). Identification of the common signaling mechanisms involved in GPCR-induced EGFR...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-11-0936
更新日期:2012-06-01 00:00:00
abstract::The PI3K/AKT/mTOR pathway, which is aberrantly stimulated in many cancer cells, has emerged as a target for therapy. However, mTORC1/S6K also mediates negative feedback loops that attenuate upstream signaling. Suppression of these feedback loops opposes the growth-suppressive effects of mTOR inhibitors and leads to dr...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-14-0669
更新日期:2015-04-01 00:00:00
abstract::Nonselective inhibitors of human histone deacetylases (HDAC) are known to have antitumor activity in mice in vivo, and several of them are under clinical investigation. The first of these, Vorinostat (SAHA), has been approved for treatment of cutaneous T-cell lymphoma. Questions remain concerning which HDAC isotype(s)...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-07-2026
更新日期:2008-04-01 00:00:00
abstract::Glioma is the most common type of primary malignant brain tumor in adults. Our previous work discovered that plasma miR-454-3p may have some advantages in glioma prognosis, but the clinical significance and the regulatory mechanism of miR-454-3p in glioma have not been systematically investigated, especially regarding...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-18-0725
更新日期:2019-02-01 00:00:00
abstract::In bone metastatic lesions, osteoclasts play a key role in the development of osteolysis. Previous studies have shown that macrophage colony-stimulating factor (M-CSF) is important for the differentiation of osteoclasts. In this study, we investigated whether an inhibitor of M-CSF receptor (c-Fms) suppresses osteoclas...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-05-0313
更新日期:2006-11-01 00:00:00