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"Targeted therapy" AND breast

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https://www.readbyqxmd.com/read/27913999/the-role-of-her2-egfr-and-other-receptor-tyrosine-kinases-in-breast-cancer
#1
Jennifer L Hsu, Mien-Chie Hung
Breast cancer affects approximately 1 in 8 women, and it is estimated that over 246,660 women in the USA will be diagnosed with breast cancer in 2016. Breast cancer mortality has decline over the last two decades due to early detection and improved treatment. Over the last few years, there is mounting evidence to demonstrate the prominent role of receptor tyrosine kinases (RTKs) in tumor initiation and progression, and targeted therapies against the RTKs have been developed, evaluated in clinical trials, and approved for many cancer types, including breast cancer...
December 2, 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27905893/computational-prediction-of-multidisciplinary-team-decision-making-for-adjuvant-breast-cancer-drug-therapies-a-machine-learning-approach
#2
Frank P Y Lin, Adrian Pokorny, Christina Teng, Rachel Dear, Richard J Epstein
BACKGROUND: Multidisciplinary team (MDT) meetings are used to optimise expert decision-making about treatment options, but such expertise is not digitally transferable between centres. To help standardise medical decision-making, we developed a machine learning model designed to predict MDT decisions about adjuvant breast cancer treatments. METHODS: We analysed MDT decisions regarding adjuvant systemic therapy for 1065 breast cancer cases over eight years. Machine learning classifiers with and without bootstrap aggregation were correlated with MDT decisions (recommended, not recommended, or discussable) regarding adjuvant cytotoxic, endocrine and biologic/targeted therapies, then tested for predictability using stratified ten-fold cross-validations...
December 1, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27903149/obesity-and-breast-cancer-prognosis-evidence-challenges-and-opportunities
#3
Sao Jiralerspong, Pamela J Goodwin
Purpose To summarize the evidence of an association between obesity and breast cancer prognosis. Methods We reviewed the literature regarding overweight and obesity and breast cancer survival outcomes, overall and with regard to breast cancer subtypes, breast cancer therapies, biologic mechanisms, and possible interventions. We summarize our findings and provide clinical management recommendations. Results Obesity is associated with a 35% to 40% increased risk of breast cancer recurrence and death and therefore poorer survival outcomes...
December 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27902972/unravelling-site-specific-breast-cancer-metastasis-a-microrna-expression-profiling-study
#4
Willemijne A M E Schrijver, Paul J van Diest, Dutch Distant Breast Cancer Metastases Consortium, Cathy B Moelans
Distant metastasis is still the main cause of death from breast cancer. MicroRNAs (miRs) are important regulators of many physiological and pathological processes, including metastasis. Molecular breast cancer subtypes are known to show a site-specific pattern of metastases formation. In this study, we set out to determine the underlying molecular mechanisms of site-specific breast cancer metastasis by microRNA expression profiling.To identify a miR signature for metastatic breast carcinoma that could predict metastatic localization, we compared global miR expression in 23 primary breast cancer specimens with their corresponding multiple distant metastases to ovary (n=9), skin (n=12), lung (n=10), brain (n=4) and gastrointestinal tract (n=10) by miRCURY microRNA expression arrays...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902967/the-non-receptor-tyrosine-kinase-tnk2-ack1-is-a-novel-therapeutic-target-in-triple-negative-breast-cancer
#5
Xinyan Wu, Muhammad Saddiq Zahari, Santosh Renuse, Dhanashree S Kelkar, Mustafa A Bharbuiya, Pamela L Rojas, Vered Stearns, Edward Gabrielson, Pavani Malla, Saraswati Sukumar, Nupam P Mahajan, Akhilesh Pandey
Breast cancer is the most prevalent cancer in women worldwide. About 15-20% of all breast cancers do not express estrogen receptor, progesterone receptor or HER2 receptor and hence are collectively classified as triple negative breast cancer (TNBC). These tumors are often relatively aggressive when compared to other types of breast cancer, and this issue is compounded by the lack of effective targeted therapy. In our previous phosphoproteomic profiling effort, we identified the non-receptor tyrosine kinase TNK2 as activated in a majority of aggressive TNBC cell lines...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901486/triple-negative-breast-cancer-development-can-be-selectively-suppressed-by-sustaining-an-elevated-level-of-cellular-cyclic-amp-through-simultaneously-blocking-its-efflux-and-decomposition
#6
Wei Wang, Yue Li, Jessica Y Zhu, Dongdong Fang, Han-Fei Ding, Zheng Dong, Qing Jing, Shi-Bing Su, Shuang Huang
Triple negative breast cancer (TNBC) has the highest mortality among all breast cancer types and lack of targeted therapy is a key factor contributing to its high mortality rate. In this study, we show that 8-bromo-cAMP, a cyclic adenosine monophosphate (cAMP) analog at high concentration (> 1 mM) selectively suppresses TNBC cell growth. However, commonly-used cAMP-elevating agents such as adenylyl cyclase activator forskolin and pan phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) are ineffective...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899992/beside-p53-and-pten-identification-of-molecular-alterations-of-the-ras-mapk-and-pi3k-akt-signaling-pathways-in-high-grade-serous-ovarian-carcinomas-to-determine-potential-novel-therapeutic-targets
#7
Shuhui Chen, Elisa Cavazza, Catherine Barlier, Julia Salleron, Pierre Filhine-Tresarrieu, Céline Gavoilles, Jean-Louis Merlin, Alexandre Harlé
Despite great histological and molecular heterogeneity, the clinical management of high-grade ovarian carcinomas remains unspecialized. As a major subgroup, high-grade serous ovarian carcinomas (HGSOCs) require novel therapies. In addition to utilizing conventional histological prognostic markers and performing oncogenetic investigations, the molecular diagnostic method of next generation sequencing (NGS) was performed to identify 'druggable' targets that could provide access to innovative therapy. The present study was performed in 45 HGSOC patients (mean age, 59...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899970/fish-testing-of-her2-immunohistochemistry-1-invasive-breast-cancer-with-unfavorable-characteristics
#8
Stella Petroni, Lucia Caldarola, Rachele Scamarcio, Francesco Giotta, Agnese Latorre, Anita Mangia, Giovanni Simone
Diagnostic assays for human epidermal growth factor receptor 2 (HER2) expression have a high predictive value because patients with HER2-positive tumors could benefit from HER2-targeted therapy. The aim of the present study is to analyze the incidence of HER2 gene amplification in selected tumors with adverse features that scored 1+ by immunohistochemistry (IHC). For that purpose, 331 consecutive invasive breast cancers (IBCs) were tested by IHC for HER2 expression between January and December 2013, 102 of which (31%) scored 1+...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27896639/seom-clinical-guideline-for-bone-metastases-from-solid-tumours-2016
#9
C Grávalos, C Rodríguez, A Sabino, M Á Seguí, J A Virizuela, A Carmona, J Cassinello, D Isla, C Jara, M Martín
Bone metastases are common in many advanced solid tumours, being breast, prostate, thyroid, lung, and renal cancer the most prevalent. Bone metastases can produce skeletal-related events (SREs), defined as pathological fracture, spinal cord compression, need of bone irradiation or need of bone surgery, and hypercalcaemia. Patients with bone metastases experience pain, functional impairment and have a negative impact on their quality of life. Several imaging techniques are available for diagnosis of this disease...
November 28, 2016: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/27896521/pi3k-akt-mtor-role-in-breast-cancer-progression-drug-resistance-and-treatment
#10
Angel Guerrero-Zotano, Ingrid A Mayer, Carlos L Arteaga
Anti-cancer cancer-targeted therapies are designed to exploit a particular vulnerability in the tumor, which in most cases results from its dependence on an oncogene and/or loss of a tumor suppressor. Mutations in the phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway are freqcuently found in breast cancers and associated with cellular transformation, tumorigenesis, cancer progression, and drug resistance. Several drugs targeting PI3K/ATK/mTOR are currently in clinical trials, mainly in combination with endocrine therapy and anti-HER2 therapy...
November 28, 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27895746/rnai-mediated-gene-silencing-of-vascular-endothelial-growth-factor-c-suppresses-growth-and-induces-apoptosis-in-mouse-breast-cancer-in-vitro-and-in-vivo
#11
Yong-Chao Liu, Wen-Hui Ma, Yin-Lin Ge, Mei-Lan Xue, Zheng Zhang, Jin-Yu Zhang, Lin Hou, Run-Hong Mu
Vascular endothelial cell growth factor (VEGF)-C promotes tumorigenesis by allowing lymph node metastasis and lymphangiogenesis, among other actions. RNA interference (RNAi) is a novel technique for suppressing target gene expression and may increase the effectiveness of cancer treatments. The present study assessed the influence of VEGF-C RNAi on the apoptosis and proliferation of mouse breast cancer cells in vitro and in vivo. A total of three pairs of small interfering RNA (siRNA) targeting mouse VEGF-C were designed and synthesized prior to transfection into 4T1 cells via a liposomal approach...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895741/the-prognostic-significance-of-estrogen-receptor-%C3%AE-in-head-and-neck-squamous-cell-carcinoma
#12
Kresimir Grsic, Iva Ledinsky Opacic, Sanda Sitic, Marija Milkovic Perisa, Petar Suton, Bozena Sarcevic
Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer in the world. Although multimodal and targeted therapy is now used in therapeutic procedures, the survival of patients with HNSCC has remained unchanged over the last 30 years. A number of studies have demonstrated that the increased expression of intranuclear ERβ in breast, lung and colon cancer is a favorable prognostic marker associated with higher survival rates. However, the clinical significance of sex hormone receptors in HNSCC remains unclear...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27894703/over-surgery-in-breast-cancer
#13
Fiona MacNeill, Andreas Karakatsanis
Breast surgery remains the original and most effective 'targeted' therapy: excision of early cancer is curative and for more advanced disease surgery improves local disease control. However in well intentioned pursuit of cure and local disease control, some cancers are over-treated resulting in major physical and emotional morbidity. Less breast surgery is safe, as evidenced by steady reductions in mortality and local recurrence; earlier diagnosis and widespread use of systemic therapies and radiotherapy have allowed more conservative surgery...
November 25, 2016: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/27885264/deciphering-the-divergent-roles-of-progestogens-in-breast-cancer
#14
Jason S Carroll, Theresa E Hickey, Gerard A Tarulli, Michael Williams, Wayne D Tilley
Most breast cancers are driven by oestrogen receptor-α. Anti-oestrogenic drugs are the standard treatment for these breast cancers; however, treatment resistance is common, necessitating new therapeutic strategies. Recent preclinical and historical clinical studies support the use of progestogens to activate the progesterone receptor (PR) in breast cancers. However, widespread controversy exists regarding the role of progestogens in this disease, hindering the clinical implementation of PR-targeted therapies...
November 25, 2016: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/27883943/targeted-therapy-for-breast-cancer-and-molecular-mechanisms-of-resistance-to-treatment
#15
REVIEW
Guowei Gu, Derek Dustin, Suzanne Aw Fuqua
In recent years, clinical trials investigating new drugs and therapeutic combinations have led to promising advances in breast cancer therapy. Subtyping breast cancers into hormone receptor (HR) positive, epidermal growth factor receptor (HER2) positive, and triple negative breast cancer (TNBC) is currently the basis of diagnosing and treating this disease. In addition to endocrine and HER2-targeted therapies in their respective subtypes, evidence from recent preclinical studies have shown several targetable pathways that overcome resistance in the clinical setting...
November 21, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27883296/adjuvant-trastuzumab-a-10-year-overview-of-its-benefit
#16
Matteo Lambertini, Noam F Pondé, Cinzia Solinas, Evandro de Azambuja
Anti-HER2 targeted therapy is one of the key advances in the treatment of breast cancer that have occurred in the last 20 years. In the adjuvant setting, the use of trastuzumab has led to prolonged and sustained survival benefit with very little toxicity as also confirmed by the 10-year follow-up results from the pivotal trials. Despite the survival improvement, several key issues are not entirely resolved in this field. These issues have led to multiple research efforts in de-escalating or escalating the standard treatment with chemotherapy and 1 year of adjuvant trastuzumab...
November 24, 2016: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/27881582/the-expanding-role-of-the-bcl6-oncoprotein-as-a-cancer-therapeutic-target
#17
Mariano G Cardenas, Erin Oswald, Wenbo Yu, Fengtian Xue, Alexander D MacKerell, Ari M Melnick
BCL6 was initially discovered as an oncogene in B-cell lymphomas, where it drives the malignant phenotype by repressing proliferation and DNA damage checkpoints and blocking B-cell terminal differentiation. BCL6 mediates its effects by binding to hundreds of target genes, and then repressing these genes by recruiting several different chromatin modifying corepressor complexes. Structural characterization of BCL6-corepressor complexes suggested that BCL6 might be a druggable target. Accordingly a number of compounds have been designed to bind to BCL6 and block corepressor recruitment...
November 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27879682/ziyuglycoside-i-inhibits-the-proliferation-of-mda-mb-231-breast-carcinoma-cells-through-inducing-p53-mediated-g2-m-cell-cycle-arrest-and-intrinsic-extrinsic-apoptosis
#18
Xue Zhu, Ke Wang, Kai Zhang, Ting Zhang, Yongxiang Yin, Fei Xu
BACKGROUND: Due to the aggressive clinical behavior, poor outcome, and lack of effective specific targeted therapies, triple-negative breast cancer (TNBC) has currently been recognized as one of the most malignant types of tumors. In the present study, we investigated the cytotoxic effect of ziyuglycoside I, one of the major components extracted from Chinese anti-tumor herbal Radix Sanguisorbae, on the TNBC cell line MDA-MB-231. METHODS: The underlying molecular mechanism of the cytotoxic effect ziyuglycoside I on MDA-MB-231 cells was investigated with cell viability assay, flow cytometric analysis and Western blot...
November 22, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27878432/histopathologic-diagnosis-of-brain-metastases-current-trends-in-management-and-future-considerations
#19
Lien Bekaert, Evelyne Emery, Guénaëlle Levallet, Emmanuèle Lechapt-Zalcman
Confronted with brain metastases (BM), pathologists aim to rule out a primary central nervous system (CNS) tumor and to identify or verify the primary tumor site to guide the clinician to specific therapies. Apart from morphological features, ancillary immunohistochemical analysis is the most effective tool for characterizing a metastatic neoplasm of unknown origin. A limited array of antibodies is used, taking into account relevant clinical information and the known brain tropism of lung cancer, breast cancer and melanoma...
November 22, 2016: Brain Tumor Pathology
https://www.readbyqxmd.com/read/27876799/irs4-induces-mammary-tumorigenesis-and-confers-resistance-to-her2-targeted-therapy-through-constitutive-pi3k-akt-pathway-hyperactivation
#20
Gerjon J Ikink, Mandy Boer, Elvira R M Bakker, John Hilkens
In search of oncogenic drivers and mechanisms affecting therapy resistance in breast cancer, we identified Irs4, a poorly studied member of the insulin receptor substrate (IRS) family, as a mammary oncogene by insertional mutagenesis. Whereas normally silent in the postnatal mammary gland, IRS4 is found to be highly expressed in a subset of breast cancers. We show that Irs4 expression in mammary epithelial cells induces constitutive PI3K/AKT pathway hyperactivation, insulin/IGF1-independent cell proliferation, anchorage-independent growth and in vivo tumorigenesis...
November 23, 2016: Nature Communications
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