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https://www.readbyqxmd.com/read/29352646/synthesis-and-biological-evaluation-of-anti-cancer-agents-that-selectively-inhibit-her2-over-expressed-breast-cancer-cell-growth-via-down-regulation-of-her2-protein
#1
Anran Zhao, Qiaoyun Zheng, Cody M Orahoske, Nethrie D Idippily, Morgan M Ashcraft, Aicha Quamine, Bin Su
Compound JCC76 selectively inhibited the proliferation of human epidermal growth factor 2 (Her2) over-expressed breast cancer cells. In the current study, a ligand based structural optimization was performed to generate new analogs, and we identified derivatives 16 and 17 that showed improved activity and selectivity against Her2 positive breast cancer cells. A structure activity relationship (SAR) was summarized. Compounds 16 and 17 were also examined by western blot assay to check their effect on Her2 protein...
January 12, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29351901/xiap-regulation-by-mnk-links-mapk-and-nf%C3%AE%C2%BAb-signaling-to-determine-an-aggressive-breast-cancer-phenotype
#2
Myron K Evans, Michael C Brown, Joseph Geradts, Xuhui Bao, Timothy J Robinson, Mohit Kumar Jolly, Peter Vermeulen, Gregory M Palmer, Matthias Gromeier, Herbert Levine, Michael A Morse, Steven Van Laere, Gayathri R Devi
Hyperactivation of the NFκB pathway is a distinct feature of inflammatory breast cancer (IBC), a highly proliferative and lethal disease. Gene expression studies in IBC patient tissue have linked epidermal growth factor receptor (EGFR/HER2)-mediated MAPK signaling to NFκB hyperactivity, but the mechanism(s) by which this occurs remain unclear. Here, we report that the X-linked inhibitor of apoptosis protein (XIAP) plays a central role in linking these two pathways. XIAP overexpression correlated with poor prognoses in breast cancer patients and was frequently observed in untreated IBC patient primary tumors...
January 19, 2018: Cancer Research
https://www.readbyqxmd.com/read/29350568/abp-980-promising-trastuzumab-biosimilar-for-her2-positive-breast-cancer
#3
Elisavet Paplomata, Rita Nahta
Approval of the HER2-targeted antibody trastuzumab dramatically improved outcomes for patients with HER2-positive breast cancer. Multiple trastuzumab biosimilars, including ABP 980, are in clinical development. Biosimilars are not identical to the reference biologic, but exhibit equivalence and safety in analytical and clinical studies. Areas covered: A brief introduction to trastuzumab, overview of trastuzumab biosimilars, and detailed review of ABP 980 preclinical and clinical studies are included. We searched PubMed and 2016-2017 ASCO and ESMO conference proceedings for "ABP 980" or "trastuzumab biosimilar"...
January 19, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29349762/advances-in-endocrine-therapy-for-postmenopausal-metastatic-breast-cancer
#4
Lisa E Flaum, William J Gradishar
A majority of breast cancers are hormone receptor (HR) positive and are responsive to various types of hormone manipulation. Endocrine therapy is the preferred first-line therapy for patients with advanced estrogen receptor (ER) positive, HER2-negative breast cancer who do not have symptomatic visceral disease. Endocrine therapy is often continued in the second- and third-line setting, with chemotherapy deferred until tumor becomes endocrine therapy refractory and/or a visceral crisis in imminent. Therapeutic options vary based on clinical presentation and include single-agent therapies such as tamoxifen, aromatase inhibitors and fulvestrant, and combination therapies options...
2018: Cancer Treatment and Research
https://www.readbyqxmd.com/read/29349598/phase-ib-study-evaluating-safety-and-clinical-activity-of-the-anti-her3-antibody-lumretuzumab-combined-with-the-anti-her2-antibody-pertuzumab-and-paclitaxel-in-her3-positive-her2-low-metastatic-breast-cancer
#5
Andreas Schneeweiss, Tjoung-Won Park-Simon, Joan Albanell, Ulrik Lassen, Javier Cortés, Veronique Dieras, Marcus May, Christoph Schindler, Frederik Marmé, Juan Miguel Cejalvo, Maria Martinez-Garcia, Iria Gonzalez, Jose Lopez-Martin, Anja Welt, Christelle Levy, Florence Joly, Francesca Michielin, Wolfgang Jacob, Céline Adessi, Annie Moisan, Georgina Meneses-Lorente, Tomas Racek, Ian James, Maurizio Ceppi, Max Hasmann, Martin Weisser, Andrés Cervantes
Purpose To investigate the safety and clinical activity of comprehensive human epidermal growth factor receptor (HER) family receptor inhibition using lumretuzumab (anti-HER3) and pertuzumab (anti-HER2) in combination with paclitaxel in patients with metastatic breast cancer (MBC). Methods This phase Ib study enrolled 35 MBC patients (first line or higher) with HER3-positive and HER2-low (immunohistochemistry 1+ to 2+ and in-situ hybridization negative) tumors. Patients received lumretuzumab (1000 mg in Cohort 1; 500 mg in Cohorts 2 and 3) plus pertuzumab (840 mg loading dose [LD] followed by 420 mg in Cohorts 1 and 2; 420 mg without LD in Cohort 3) every 3 weeks, plus paclitaxel (80 mg/m2 weekly in all cohorts)...
January 19, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29348868/luminal-like-her2-negative-stage-ia-breast-cancer-a-multicenter-retrospective-study-on-long-term-outcome-with-propensity-score-analysis
#6
Carmine De Angelis, Massimo Di Maio, Anna Crispo, Mario Giuliano, Francesco Schettini, Marta Bonotto, Lorenzo Gerratana, Donatella Iacono, Marika Cinausero, Ferdinando Riccardi, Giuseppe Ciancia, Michelino De Laurentiis, Fabio Puglisi, Sabino De Placido, Grazia Arpino
The benefit of adding chemotherapy (CT) to adjuvant hormone therapy (HT) in stage IA luminal-like HER2-negative breast cancer (BC) is unclear. We retrospectively evaluated predictive factors and clinical outcome of 1,222 patients from 4 oncologic centers. Three hundred and eighty patients received CT and HT (CT-cohort) and 842 received HT alone (HT-cohort). Disease-free survival (DFS) and overall survival (OS) were evaluated with univariate and multivariate analyses. We also applied the propensity score methodology...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348822/the-localization-of-pre-mrna-splicing-factor-prpf38b-is-a-novel-prognostic-biomarker-that-may-predict-survival-benefit-of-trastuzumab-in-patients-with-breast-cancer-overexpressing-her2
#7
Tarek M A Abdel-Fatah, Robert C Rees, A Graham Pockley, Paul Moseley, Graham R Ball, Stephen Y T Chan, Ian O Ellis, Amanda K Miles
Cancer biomarkers that can define disease status and provide a prognostic insight are essential for the effective management of patients with breast cancer (BC). The prevalence, clinicopathological and prognostic significance of PRPF38B expression in a consecutive series of 1650 patients with primary invasive breast carcinoma were examined using immunohistochemistry. Furthermore, the relationship(s) between clinical outcome and PRPF38B expression was explored in 627 patients with ER-negative (oestrogen receptor) disease, and 322 patients with HER2-overexpressing disease...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29345736/palbociclib-in-combination-with-letrozole-as-first-line-treatment-for-advanced-breast-cancer-a-japanese-phase-ii-study
#8
Norikazu Masuda, Reiki Nishimura, Masato Takahashi, Kenichi Inoue, Shinji Ohno, Hiroji Iwata, Yuko Mori, Satoshi Hashigaki, Yasuaki Muramatsu, Takashi Nagasawa, Yoshiko Umeyama, Masakazu Toi
This single-arm, open-label, phase II study in 42 Japanese postmenopausal patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer evaluated the efficacy, safety, and pharmacokinetics of first-line palbociclib (125 mg once daily, 3 weeks on/1 week off) coadministered with letrozole (2.5 mg once daily). The primary endpoint of investigator-assessed 1-year progression-free survival probability was 75.0% (90% CI, 61.3%-84.4%), far surpassing the 40% lower limit of the 90% CI supporting efficacy...
January 18, 2018: Cancer Science
https://www.readbyqxmd.com/read/29345357/the-prognostic-value-of-pi3k-mutational-status-in-breast-cancer-a-meta-analysis
#9
N Sobhani, G Roviello, S P Corona, M Scaltriti, A Ianza, M Bortul, F Zanconati, D Generali
Breast cancer (BC) is the second most common cause of cancer-related deaths in women worldwide. The availability of reliable biomarkers of response/resistance to cancer treatments would benefit patients and clinicians allowing for a better selection of BC patients most likely to respond to a specific treatment. Phosphatidylinositol 3-kinase (PI3K) enzymes are involved in numerous cellular- functions and processes. The gene encoding for PI3K catalytic subunit p110α is mutated in 20-40% of BC. We performed a meta-analysis of the current literature on randomized clinical trials, investigating the role of PIK3CA mutational status as prognostic factor and predictor of response to anti-cancer treatments...
January 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29345338/miat-lncrna-is-overexpressed-in-breast-cancer-and-its-inhibition-triggers-senescence-and-g1-arrest-in-mcf7-cell-line
#10
Firooz Jannat Alipoor, Malek Hossein Asadi, Masoud Torkzadeh-Mahani
Long non-coding RNAs are known as key regulators in the progression and metastasis of breast cancer. Miat originally has been considered as an lncRNA to be associated with a susceptibility to myocardial infarction. Here, we have detected the expression of Miat in different cancer cells and a series of breast tumor tissue. Miat expression was much higher in high-grade tumors compared to low-grade ones. Unlike P53 positive tumors, Miat expression was upregulated in ER, PR, Her2 positive tumor tissues. Knockdown Miat suppressed breast cancer cell proliferation and caused G1 arrest in cell cycle...
January 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29344282/clinical-significance-of-glycoprotein-non-metastatic-b-and-its-association-with-egfr-her2-in-gastrointestinal-cancer
#11
Jesse Yu Tajima, Manabu Futamura, Siqin Gaowa, Ryutaro Mori, Toshiyuki Tanahashi, Yoshihiro Tanaka, Nobuhisa Matsuhashi, Takao Takahashi, Kazuya Yamaguchi, Tatsuhiko Miyazaki, Kazuhiro Yoshida
Glycoprotein non-metastatic B (GPNMB), a type I transmembrane glycoprotein, is overexpressed in melanoma and breast cancer and promotes cancer-cell invasion and motility. We previously reported cross-talk between GPNMB and human epidermal growth factor receptor 2 (HER2) in breast cancer, suggesting that GPNMB might play an important role in resistance to anti-HER2 therapy in breast cancer. Here, we clarified the association between GPNMB and HER-family proteins in gastrointestinal cancer by examining their relationships using gastric and colorectal cancer cell lines...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29344106/overall-survival-and-progression-free-survival-with-endocrine-therapy-for-hormone-receptor-positive-her2-negative-advanced-breast-cancer-review
#12
REVIEW
Tomás Reinert, Carlos H Barrios
We reviewed randomized phase II/III trials comparing first- or second-line endocrine therapy as monotherapy or in combination with targeted therapies for treatment of postmenopausal patients with hormone receptor-positive advanced breast cancer. First-line was defined as treatment for endocrine therapy-naïve advanced breast cancer or advanced disease treated with endocrine therapy in the adjuvant/neoadjuvant setting. Second-line was defined as endocrine therapy for advanced breast cancer following disease progression on endocrine therapy for advanced disease...
November 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29340880/gata-3-is-superior-to-gcdfp-15-and-mammaglobin-to-identify-primary-and-metastatic-breast-cancer
#13
Yun-Bi Ni, Julia Y S Tsang, Mu-Min Shao, Siu-Ki Chan, Sai-Yin Cheung, Joanna Tong, Ka-Fai To, Gary M Tse
PURPOSE: Despite numerous studies on the utility of GATA-3 as breast cancer marker, its comparison with other breast markers, its concordance between primary and metastatic tumors and its expression in primary cancers from sites with frequent breast metastases remains unclear. METHODS: To address these questions, totally 993 invasive breast cancers (IBC), 254 paired nodal metastases, 23 distant metastases, and 208 lung carcinomas were included. GATA-3 expression was analyzed by immunohistochemistry and compared to other breast markers [gross cystic disease fluid protein 15 (GCDFP-15) and mammaglobin (MGB)]...
January 16, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29340066/clinicopathological-and-prognostic-significance-of-sdc1-overexpression-in-breast-cancer
#14
Xiangrong Cui, Xuan Jing, Qin Yi, Chunlan Long, Jie Tian, Jing Zhu
Background: Breast cancer is the leading cause of cancer death among global women, and its early diagnosis and treatment are very urgent. Syndecan-1 (SDC1) is a heparin sulfate proteoglycan, which has been linked with the prognosis and treatment response in a various tumor type. To investigate whether SDC1 can serve as a prognostic indictor in breast cancer, bioinformatic analyses were performed in the present study. Methods: SDC1 expression was assessed using Oncomine analysis...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340027/dual-sirt1-expression-patterns-strongly-suggests-its-bivalent-role-in-human-breast-cancer
#15
Khaldoun Rifaï, Gaëlle Judes, Mouhamed Idrissou, Marine Daures, Yves-Jean Bignon, Frédérique Penault-Llorca, Dominique Bernard-Gallon
Breast cancer is the most common cancer in women, and the leading cause of cancer death in women worldwide. SIRT1 (silent mating type information regulation 2 homolog) 1 is a class-III histone deacetylase involved in apoptosis regulation, DNA repair and tumorigenesis. However, its role in breast carcinoma remains controversial, as both tumor-suppressive and tumor-promoting functions have been reported. Also, there are very few reports available where expression of SIRT1 is comprehensively analyzed in breast tumors classified by molecular subtype...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29338072/targeting-her2-in-colorectal-cancer-the-landscape-of-amplification-and-short-variant-mutations-in-erbb2-and-erbb3
#16
Jeffrey S Ross, Marwan Fakih, Siraj M Ali, Julia A Elvin, Alexa B Schrock, James Suh, Jo-Anne Vergilio, Shakti Ramkissoon, Eric Severson, Sugganth Daniel, David Fabrizio, Garrett Frampton, James Sun, Vincent A Miller, Philip J Stephens, Laurie M Gay
BACKGROUND: In contrast to lung cancer, few precision treatments are available for colorectal cancer (CRC). One rapidly emerging treatment target in CRC is ERBB2 (human epidermal growth factor receptor 2 [HER2]). Oncogenic alterations in HER2, or its dimerization partner HER3, can underlie sensitivity to HER2-targeted therapies. METHODS: In this study, 8887 CRC cases were evaluated by comprehensive genomic profiling for genomic alterations in 315 cancer-related genes, tumor mutational burden, and microsatellite instability...
January 16, 2018: Cancer
https://www.readbyqxmd.com/read/29337140/characteristics-and-prognostic-factors-for-patients-with-her2-overexpressing-breast-cancer-and-brain-metastases-in-the-era-of-her2-targeted-therapy-an-argument-for-earlier-detection
#17
Aki Morikawa, Rui Wang, Sujata Patil, Adi Diab, Jonathan Yang, Clifford A Hudis, Heather L McArthur, Kathryn Beal, Andrew D Seidman
BACKGROUND: Although brain metastases (BM) are associated with poor prognosis, patients with human epidermal growth factor receptor 2 (HER2) overexpressing (HER2+) breast cancer (BC) with BM who are treated with anti-HER2 therapy have a relatively longer survival after BM diagnosis compared with other subtypes and HER2+ patients previously untreated with anti-HER2 therapy. It is unclear if previously reported prognostic factors are applicable to patients with HER2+ BC in the era of HER2-targeted therapy...
December 21, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29336662/body-mass-index-in-her2-negative-metastatic-breast-cancer-treated-with-first-line-paclitaxel-and-bevacizumab
#18
Laura Pizzuti, Domenico Sergi, Isabella Sperduti, Luigi Di Lauro, Marco Mazzotta, Claudio Botti, Fiorentino Izzo, Luca Marchetti, Silverio Tomao, Paolo Marchetti, Clara Natoli, Antonino Grassadonia, Teresa Gamucci, Lucia Mentuccia, Emanuela Magnolfi, Angela Vaccaro, Alessandra Cassano, Ernesto Rossi, Andrea Botticelli, Valentina Sini, Maria G Sarobba, Maria Agnese Fabbri, Luca Moscetti, Antonio Astone, Andrea Michelotti, Claudia De Angelis, Ilaria Bertolini, Francesco Angelini, Gennaro Ciliberto, Marcello Maugeri-Saccà, Antonio Giordano, Maddalena Barba, Patrizia Vici
The evidence emerged from the TOURANDOT trial encourages evaluating the role of anthropometric determinants on treatment outcomes in HER2-negative metastatic breast cancer patients treated with bevacizumab-including regimens. We thus analyzed data from a subgroup of these patients from a larger cohort previously assessed for treatment outcomes. Patients were included in the present analysis if body mass index values had been recorded at baseline. Clinical benefit rates, progression free survival and overall survival were assessed for the overall study population and subgroups defined upon molecular subtype...
January 16, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29336321/epstein-barr-virus-and-invasive-mammary-carcinomas-ebna-ebers-and-molecular-profile-in-a-population-of-west-algeria
#19
Radia Yahia, Chahinez Zaoui, Wafaa Derbale, Hafsa Boudi, Yahia Chebloune, Tewfik Sahraoui, Fatima Zohra Elkebir
Breast cancer is the common malignancy that affects women worldwide, but conventional risk factors account for only a small proportion of these cases. A possible viral etiology for breast cancer has been proposed and Epstein-Barr virus (EBV) is a widely studied candidate virus. The objective of this study is to determine the association of EBV infection with infiltrating ductal carcinomas (IDC). This descriptive study was carried out in the laboratory of developmental biology and differentiation, from 2012 to 2014...
January 16, 2018: Annales de Biologie Clinique
https://www.readbyqxmd.com/read/29336185/an-update-on-first-line-therapies-for-metastatic-breast-cancer
#20
Palma Fedele, Mariangela Ciccarese, Giammarco Surico, Saverio Cinieri
In recent years, outcomes of patients with metastatic breast cancer (MBC) have improved due to a greater understanding of the mechanisms of carcinogenesis in the development of newer molecularly targeted drugs, especially those as a front-line therapy. Remarkable improvements have been made in the treatment of hormone receptor positive (HR+) and Her2 positive MBC and currently targeted treatment strategies represent a valid first line treatment. Areas covered: Herein, the authors provide an overview of the first-line pharmacotherapies currently available for the treatment of MBC and provide their expert perspectives on the area...
January 16, 2018: Expert Opinion on Pharmacotherapy
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