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Targeted therapy in breast cancer

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https://www.readbyqxmd.com/read/28815913/metastatic-triple-negative-breast-cancer-optimizing-treatment-options-new-and-emerging-targeted-therapies
#1
REVIEW
Parham Khosravi-Shahi, Luis Cabezón-Gutiérrez, Sara Custodio-Cabello
Triple negative breast cancer (TNBC) is a heterogeneous disease, not only on the molecular level, but also on the pathologic and clinical levels. It also has a distinct epidemiology. TNBCs are frequently of high histologic grade, typically more aggressive and difficult to treat than hormone receptor-positive tumors, and they are associated with a higher risk of early relapse with visceral metastasis after surgery, chemotherapy and/or radiotherapy. The lack of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 expression precludes the use of targeted therapies in advanced stages, and the only approved systemic treatment option is chemotherapy with or without bevacizumab...
August 16, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28815041/-upregulation-of-cd47-by-the-endoplasmic-reticulum-stress-pathway-controls-anti-tumor-immune-responses
#2
Katherine L Cook, David R Soto-Pantoja
We recently demonstrated that targeting the unfolded protein response (UPR) protein GRP78 down-regulates CD47 expression, resulting in increased tumor macrophage infiltration and inhibited resistance to anti-estrogen therapy. We now show new data indicating that anti-estrogen therapy regulates CD47 expression and implicates its ligand, thrombospondin-1, in regulation of tumor macrophage infiltration. Moreover, GRP78 and CD47 co-expression is associated with poor prognosis in breast cancer patients, suggesting the existence of crosstalk between UPR and immunity that regulates therapeutic responses in breast cancer...
2017: Biomarker Research
https://www.readbyqxmd.com/read/28814897/discordance-of-the-estrogen-receptor-and-her-2-neu-in-breast-cancer-from-primary-lesion-to-first-and-second-metastatic-site
#3
Elyse E Lower, Shagufta Khan, Diane Kennedy, Robert P Baughman
BACKGROUND: Hormone receptor and HER-2/neu discordance between the primary lesion and first metastasis has been reported. This study was performed to determine further biomarker discordance rates between the first and subsequent metastatic breast cancer lesions. METHODS: We performed a retrospective review of paired biomarkers from primary breast cancers compared to first reported and subsequent metastases from 103 patients with breast cancer. The estrogen receptor (ER), progesterone receptor (PR), and HER-2/neu status were reported at all three time points...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28814238/structural-insights-for-drugs-developed-for-phospholipase-d-enzymes
#4
Kimberly Stieglitz
BACKGROUND: In recent years human phospholipase D enzymes (PLD1 and PLD2 isozymes) have emerged as drug targets for various diseases such as cardiovascular disease, cancer, infectious diseases and neurodegenerative conditions such as Alzheimer's and Parkinson's disease. The interest in PLD as a drug target is due to the fact that PLD enzymes belong to a superfamily of phospholipases that are essential to intracellular and extracellular signaling. Many bioactive lipid signaling molecules are generated by these enzymes including phosphatidic and lysophosphatidic acid, arachidonic acid, and diacylglycerol (DAG)...
August 15, 2017: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/28811325/ppar%C3%AE-ligand-induced-annexin-a1-expression-determines-chemotherapy-response-via-deubiquitination-of-death-domain-kinase-rip-in-triple-negative-breast-cancers
#5
Luxi Chen, Yi Yuan, Shreya Kar, Madhu M Kanchi, Suruchi Arora, Ji E Kim, Pei F Koh, Einas Yousef, Ramar P Samy, Muthu K Shanmugam, Tuan Z Tan, Sung W Shin, Frank Arfuso, Han M Shen, Henry Yang, Boon C Goh, Joo I Park, Louis Gaboury, Peter E Lobie, Gautam Sethi, Lina Hk Lim, Alan P Kumar
Metastatic breast cancer is still remain incurable so far, new specifically targeted and more effective therapies for triple negative breast cancer (TNBC) are required in the clinic. In this study, our clinical data has established that basal and claudin-low subtypes of breast cancer (TNBC types) express significantly higher levels of Annexin A1 (ANXA1) with poor survival outcomes. Using human cancer cell lines which model the TNBC subtype, we observed a strong positive correlation between expression of ANXA1 and Peroxisome Proliferator-Activated Receptor gamma (PPARγ)...
August 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28810532/plga-ctab-curcumin-nanoparticles-fabrication-characterization-and-molecular-basis-of-anticancer-activity-in-triple-negative-breast-cancer-cell-lines-mda-mb-231-cells
#6
Ramovatar Meena, Sumit Kumar, Raj Kumar, Usha Singh Gaharwar, Paulraj Rajamani
Triple-negative breast cancers (TNBC) are aggressive cancers, which do not control by hormonal therapy or therapies that target HER-2 receptors. Curcumin (Cur) has shown cytotoxic effects in multiple cancer cell lines. However, its medical uses remain limited due to low aqueous solubility and poor bioavailability. Therefore, present study was aimed to fabricate the small positive charge curcumin nanoparticles (CN) by nanoprecipitation methods using PLGA and CTAB, and to evaluate its anticancer efficacy and underlying the mechanism in triple negative breast cancer cell lines (MDA-MB-231 cells)...
August 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28807940/mitotic-vulnerability-in-triple-negative-breast-cancer-associated-with-lin9-is-targetable-with-bet-inhibitors
#7
Jennifer M Sahni, Sylvia S Gayle, Bryan Webb, Kristen L Weber-Bonk, Darcie D Seachrist, Salendra Singh, Steven T Sizemore, Nicole A Restrepo, Gurkan Bebek, Peter Scacheri, Vinay Varadan, Matthew K Summers, Ruth A Keri
Triple-negative breast cancers (TNBC) are highly aggressive, lack FDA-approved targeted therapies, and frequently recur, making the discovery of novel therapeutic targets for this disease imperative. Our previous analysis of the molecular mechanisms of action of Bromodomain and extraterminal protein inhibitors (BETi) in TNBC revealed these drugs cause multinucleation, indicating BET proteins are essential for efficient mitosis and cytokinesis. Here, using live cell imaging, we show that BET inhibition prolonged mitotic progression and induced mitotic cell death, both of which are indicative of mitotic catastrophe...
August 14, 2017: Cancer Research
https://www.readbyqxmd.com/read/28807690/synergistic-effect-of-quercetin-and-ph-responsive-deae-chitosan-carriers-as-drug-delivery-system-for-breast-cancer-treatment
#8
Rafael de Oliveira Pedro, Francisco M Goycoolea, Susana Pereira, Carla C Schmitt, Miguel G Neumann
Amphiphilic chitosans, which may self-assemble in aqueous solution to form nanoaggregates with different conformations depending to the environmental pH, can be used as drug transport and delivery agents, when the target pH differs from the delivery medium pH. In this study, quercetin, a bioactive flavonoid, was encapsulated in a pH-responsive system based on amphiphilic chitosan. The hydrophilic reagent 2-chloro-N,N-diethylethylamine hydrochloride (DEAE), also known to inhibit the proliferation of cancer cells, was used as a grafting agent...
August 11, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28803675/the-yale-fitness-intervention-trial-in-female-cancer-survivors-cardiovascular-and-physiological-outcomes
#9
M Tish Knobf, Sangchoon Jeon, Barbara Smith, Lyndsay Harris, Siobhan Thompson, Mitchel R Stacy, Karl Insogna, Albert J Sinusas
BACKGROUND: Induced premature menopause and cardio-toxic therapy increase cardiovascular disease risk in female cancer survivors. OBJECTIVE: To compare the effects of a 12 month aerobic-resistance fitness center intervention to home based physical activity on cardiovascular function and metabolic risk factors. METHODS: Subjects (N = 154) who had completed primary and/or adjuvant chemotherapy (past 3 years) were randomized to a fitness center intervention or a home based group...
August 10, 2017: Heart & Lung: the Journal of Critical Care
https://www.readbyqxmd.com/read/28801156/alarming-burden-of-triple-negative-breast-cancer-in-india
#10
REVIEW
Krishan K Thakur, Devivasha Bordoloi, Ajaikumar B Kunnumakkara
Breast cancer is the most prevalent cancer among women worldwide. Among the different breast cancer subtypes, triple-negative breast cancer (TNBC), which is more prevalent among younger age women, is the most aggressive form. Numerous clinicopathologic studies performed throughout the world strongly support the utterly poor prognoses and high recurrence rate of TNBC. The present report details a thorough data survey from Google and PubMed on the burden of TNBC worldwide and other associated factors, with special emphasis on its ever increasing incidence among Indian women...
July 20, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28800870/recent-advances-in-her2-positive-breast-cancer-epigenetics-susceptibility-and-therapeutic-strategies
#11
REVIEW
Heena Singla, Abhilash Ludhiadch, Raman Preet Kaur, Harish Chander, Vinod Kumar, Anjana Munshi
HER2 amplification/overexpression accounts for aggressive clinical features of HER2 positive breast cancer. Epigenetic changes including DNA methylation, histone modifications and ncRNAs/miRNAs are associated with regulation of DNA chromatin and specifically, gene transcription. Hence, these produce eminent effects upon proto-oncogenes, tumor-suppressors and key cancer-regulatory signaling pathways. Understanding of epigenomic regulation of HER2 overexpression and signaling may help uncover the unmatchable physiology of HER2 gene/protein...
August 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28800861/ipatasertib-plus-paclitaxel-versus-placebo-plus-paclitaxel-as-first-line-therapy-for-metastatic-triple-negative-breast-cancer-lotus-a-multicentre-randomised-double-blind-placebo-controlled-phase-2-trial
#12
Sung-Bae Kim, Rebecca Dent, Seock-Ah Im, Marc Espié, Sibel Blau, Antoinette R Tan, Steven J Isakoff, Mafalda Oliveira, Cristina Saura, Matthew J Wongchenko, Amy V Kapp, Wai Y Chan, Stina M Singel, Daniel J Maslyar, José Baselga
BACKGROUND: The oral AKT inhibitor ipatasertib is being investigated in cancers with a high prevalence of PI3K/AKT pathway activation, including triple-negative breast cancer. The LOTUS trial investigated the addition of ipatasertib to paclitaxel as first-line therapy for triple-negative breast cancer. METHODS: In this randomised, placebo-controlled, double-blind, phase 2 trial, women aged 18 years or older with measurable, inoperable, locally advanced or metastatic triple-negative breast cancer previously untreated with systemic therapy were recruited from 44 hospitals in South Korea, the USA, France, Spain, Taiwan, Singapore, Italy, and Belgium...
August 8, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28800545/liver-toxicity-of-chemotherapy-and-targeted-therapy-for-breast-cancer-patients-with-hepatitis-virus-infection
#13
Yu Liu, Zhan-Yi Li, Xi Li, Jia-Ni Wang, Qun-Ai Huang, Yong Huang
BACKGROUND: Chemotherapy has greatly improved the prognosis of breast cancer patients. However, it may also result in undesirable side effects such as hepatitis virus reactivation. Little information is available on the liver toxicity of chemotherapy and targeted therapy for breast cancer patients with hepatitis virus (HBV/HCV) infection. METHODS: We performed a retrospective survey of 835 patients diagnosed with breast cancer between January 2010 and December 2015 at our institution...
August 8, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28799743/reducing-interstitial-fluid-pressure-ifp-and-inhibiting-pulmonary-metastasis-of-breast-cancer-by-gelatin-modified-cationic-lipid-nanoparticles
#14
Xuan Gao, Jun Zhang, Zun Huang, Tiantian Zuo, Qing Lu, Guangyu Wu, Qi Shen
Interstitial fluid pressure (IFP) in tumor is much higher than that in normal tissue and it constitutes a great obstacle for the delivery of anti-tumor drugs, which makes it a potential target for cancer therapy. In this study, cationic nanostructured lipid carriers (NLCs) were modified by gelatin with low molecular weight in order to achieve the desirable reduction of tumor IFP and improve the drug delivery as well as the chemotherapy on tumor proliferation and pulmonary metastasis. The nanoparticles were used to entrap three drugs - docetaxel (DTX), quercetin (Qu) and imatinib (IMA) - with high encapsulation efficiency of 89...
August 11, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28799567/identification-of-breast-cancer-mechanism-based-on-weighted-gene-coexpression-network-analysis
#15
X Guo, H Xiao, S Guo, L Dong, J Chen
Our gene expression-profiling analysis aimed to explain the mechanism of breast cancer development by identifying key pathways and constructing networks of related transcription factors (TFs) and microRNAs (miRNAs) in breast cancer tissues. Gene expression profiles of normal and breast cancer tissues were downloaded to identify differentially expressed genes (DEGs). Coexpression modules were explored using weighted gene coexpression network analysis (WGCNA). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to discover the enriched functionally associated gene groups and define pathways in breast cancer, respectively...
August 11, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28799073/immunotherapy-in-breast-cancer-the-emerging-role-of-pd-1-and-pd-l1
#16
REVIEW
François Bertucci, Anthony Gonçalves
PURPOSE OF REVIEW: The purpose of the review is to summarize the data regarding PD-L1 expression in breast cancer and the results of first clinical trials with PD-1 or PD-L1 inhibitors in patients with metastatic breast cancer. RECENT FINDINGS: PD-L1 expression is heterogeneous across primary breast cancers, and is generally associated with the presence of tumor-infiltrating lymphocytes and the presence of poor-prognosis features such as high grade, and aggressive molecular subtypes (triple-negative (TN), basal, HER2-enriched)...
August 10, 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28798274/disparities-of-trastuzumab-use-in-resource-limited-or-resource-abundant-regions-and-its-survival-benefit-on-her2-positive-breast-cancer-a-real-world-study-from-china
#17
Jianbin Li, Shusen Wang, Yongsheng Wang, Xiaojia Wang, Haibo Wang, Jifeng Feng, Qingyuan Zhang, Tao Sun, Quchang Ouyang, Yongmei Yin, Yinhua Liu, Cuizhi Geng, Min Yan, Zefei Jiang
BACKGROUND: Trastuzumab is a key component of therapy for human epidermal growth receptor 2 (HER2) positive breast cancer. Because real-world data are lacking, the present research was conducted to evaluate the the actual use of and the effectiveness of trastuzumab in the real world in China. METHODS: Inpatients with HER2 positive invasive breast cancer from 13 hospitals in Eastern China (2010-2015, n = 1,139) were included in this study. We aimed to assess the actual use of trastuzumab and to evaluate potential efficacy from trastuzumab in real-world research...
August 10, 2017: Oncologist
https://www.readbyqxmd.com/read/28794644/the-rank-rankl-opg-system-in-tumorigenesis-and-metastasis-of-cancer-stem-cell-potential-targets-for-anticancer-therapy
#18
REVIEW
Mekonnen Sisay, Getnet Mengistu, Dumessa Edessa
The molecular triad involving receptor activator of nuclear factor kβ (RANK)/RANK ligand (RANKL)/osteoprotegerin cytokine system has been well implicated in several physiological and pathological processes including bone metabolism, mammary gland development, regulation of the immune function, tumorigenesis and metastasis of cancer stem cell, thermoregulation, and vascular calcification. However, this review aimed to summarize several original and up-to-date articles focusing on the role of this signaling system in cancer cell development and metastasis as well as potential therapeutic agents targeting any of the three tumor necrotic factor super family proteins and/or their downstream signaling pathways...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28791634/targeting-her2-in-advanced-breast-cancer
#19
Xiaofu Zhu, Anil Abraham Joy
Human epidermal growth factor receptor 2 (HER2) is a human oncogene that is amplified in approximately 20% of breast cancers, and portends a worse prognosis if not treated with anti-HER2 agents. The advent of targeted anti-HER2 therapies has dramatically improved disease control and survival in patients with metastatic HER2-positive breast cancer, and is now considered standard of care in the first-line setting and beyond. This review summarizes the currently available data on targeted anti-HER2 therapies from completed randomized phase III clinical trials, and briefly discusses emerging advances that will address unmet needs in metastatic HER2-positive breast cancer...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28791631/erbb-receptors-and-cancer
#20
Zhixiang Wang
The ErbB receptor family, also known as the EGF receptor family or type I receptor family, includes the epidermal growth factor (EGF) receptor (EGFR) or ErbB1/Her1, ErbB2/Her2, ErbB3/Her3, and ErbB4/Her4. Among all RTKs, EGFR was the first RTK identified and the first one linked to cancer. Thus, EGFR has also been the most intensively studied among all RTKs. ErbB receptors are activated after homodimerization or heterodimerization. The ErbB family is unique among the various groups of receptor tyrosine kinases (RTKs) in that ErbB3 has impaired kinase activity, while ErbB2 does not have a direct ligand...
2017: Methods in Molecular Biology
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