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"Targeted therapy" AND breast

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https://www.readbyqxmd.com/read/28522586/antitumor-synergism-and-enhanced-survival-with-a-tumor-vasculature-targeted-enzyme-prodrug-system-rapamycin-and-cyclophosphamide
#1
John J Krais, Needa Virani, Partick H McKernan, Quang Nguyen, Kar-Ming Fung, Vassilios I Sikavitsas, Carla D Kurkjian, Roger G Harrison
Mutant cystathionine gamma-lyase was targeted to phosphatidylserine exposed on tumor vasculature through fusion with annexin A1 or annexin A5.  Cystathionine gamma-lyase E58N, R118L, and E338N mutations impart non-native methionine gamma-lyase activity, resulting in tumor-localized generation of highly toxic methylselenol upon systemic administration of non-toxic selenomethionine.  The described therapeutic system circumvents systemic toxicity issues using a novel drug delivery/generation approach and avoids the administration of non-native proteins and/or DNA required with other enzyme prodrug systems...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28521178/impact-of-2013-asco-cap-guidelines-on-her2-determination-of-invasive-breast-cancer-a-single-institution-experience-using-frontline-dual-color-fish
#2
M Ragazzi, A Bisagni, E Gasparini, E Kuhn, C Bassano, I Tamagnini, M Foroni, M Bortesi, G Falco, G Ferrari, L Braglia, L Savoldi, A Bologna, R Di Cicilia, G Bisagni, G Gardini
PURPOSE: The new ASCO/CAP guidelines published in 2013 (AC2013) significantly modified the scoring criteria for HER2-FISH, introducing the most controversial change to the HER2-equivocal category. We retrospectively evaluated the impact of AC2013 in a cohort of consecutive invasive breast cancers (IBCs) analyzed with frontline dual-color FISH. METHODS: 2788 consecutive IBCs were reclassified based on the AC2013 guidelines. Clinico-pathological features of equivocal IBCs were compared with HER2-negative and HER2-positive IBCs...
May 15, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28515445/protein-kinase-c-inhibitor-chelerythrine-selectively-inhibits-proliferation-of-triple-negative-breast-cancer-cells
#3
Wanjun Lin, Jiajun Huang, Zhongwen Yuan, Senling Feng, Ying Xie, Wenzhe Ma
Triple-negative breast cancer (TNBC) is a subtype of breast cancer lacking targeted therapy currently. Recent studies imply that protein kinase C may play important roles in TNBC development and could be a specific target. In this study, we evaluated the anti-proliferative activity of PKC inhibitor chelerythrine on a panel of breast cancer cell lines. Chelerythrine selectively inhibited the growth of TNBC cell lines compared to non-TNBC cell lines as demonstrated by in vitro cell proliferation assay and colony formation assay, as well as evidenced by in vivo xenograft assay...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28514727/nuclear-receptor-nr4a1-is-a-tumor-suppressor-down-regulated-in-triple-negative-breast-cancer
#4
Hongmei Wu, Jiong Bi, Yan Peng, Lei Huo, Xiaobin Yu, Zhihui Yang, Yunyun Zhou, Li Qin, Yixiang Xu, Lan Liao, Yang Xie, Orla M Conneely, Jos Jonkers, Jianming Xu
The nuclear receptor (NR) superfamily contains hormone-inducible transcription factors that regulate many physiological and pathological processes through regulating gene expression. NR4A1 is an NR family member that still does not have an identified endogenous ligand, and its role in cancer is also currently unclear and controversial. In this study, we aimed to define the expression profiles and specific role of NR4A1 in the highly malignant triple-negative breast cancer (TNBC), which still lacks available targeted therapies...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28514302/safety-and-efficacy-evaluation-of-pertuzumab-in-patients-with-solid-tumors
#5
Chenjing Zhu, Wenwu Ling, Jing Zhang, Hui Gao, Kai Shen, Xuelei Ma
BACKGROUND: The development of targeted therapies benefits patients with certain markers in the treatment of breast cancer. Pertuzumab is a novel humanized monoclonal antibody that blocks human epidermal growth factor receptor 2 (HER2) dimerization. The Food and Drug Administration has approved pertuzumab in combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer. METHODS: To assess the safety and efficacy profile of pertuzumab, we searched PubMed and Embase (articles from January 1966 to January 2015) using the keyword "pertuzumab"...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28513565/epidermal-growth-factor-receptor-cell-proliferation-signaling-pathways
#6
REVIEW
Ping Wee, Zhixiang Wang
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is commonly upregulated in cancers such as in non-small-cell lung cancer, metastatic colorectal cancer, glioblastoma, head and neck cancer, pancreatic cancer, and breast cancer. Various mechanisms mediate the upregulation of EGFR activity, including common mutations and truncations to its extracellular domain, such as in the EGFRvIII truncations, as well as to its kinase domain, such as the L858R and T790M mutations, or the exon 19 truncation...
May 17, 2017: Cancers
https://www.readbyqxmd.com/read/28512267/exploratory-investigation-of-psca-protein-expression-in-primary-breast-cancer-patients-reveals-a-link-to-her2-neu-overexpression
#7
Theresa Link, Friederike Kuithan, Armin Ehninger, Jan Dominik Kuhlmann, Michael Kramer, Andreas Werner, Axel Gatzweiler, Barbara Richter, Gerhard Ehninger, Gustavo Baretton, Michael Bachmann, Pauline Wimberger, Katrin Friedrich
BACKGROUND: Prostate stem cell antigen (PSCA) has been suggested as biomarker and therapeutic target for prostate cancer. Recent advances showed that PSCA is up-regulated in other cancer entities, such as bladder or pancreatic cancer. However, the clinical relevance of PSCA-expression in breast cancer patients has not yet been established and is therefore addressed by the current study. METHODS: PSCA-protein expression was assessed in 405 breast cancer patients, using immunohistochemistry (PSCA antibody MB1) and tissue microarrays...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28512248/androgen-receptor-supports-an-anchorage-independent-cancer-stem-cell-like-population-in-triple-negative-breast-cancer
#8
Valerie N Barton, Jessica L Christenson, Michael A Gordon, Lisa I Greene, Thomas J Rogers, Kiel Butterfield, Beatrice Babbs, Nicole S Spoelstra, Nicholas C D'Amato, Anthony Elias, Jennifer K Richer
Preclinical and early clinical trials indicate that up to 50% of triple-negative breast cancers (TNBC) express androgen receptor (AR) and are potentially responsive to anti-androgens. However, the function of AR in TNBC and the mechanisms by which AR-targeted therapy reduces tumor burden are largely unknown. We hypothesized that AR maintains a cancer stem cell (CSC)-like tumor initiating population and serves as an anti-apoptotic factor, facilitating anchorage independence and metastasis. AR levels increased in TNBC cells grown in forced suspension culture compared to those in attached conditions, and cells that expressed AR resisted detachment-induced apoptosis...
May 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28508872/actin-stress-fiber-organization-promotes-cell-stiffening-and-proliferation-of-pre-invasive-breast-cancer-cells
#9
Sandra Tavares, André Filipe Vieira, Anna Verena Taubenberger, Margarida Araújo, Nuno Pimpao Martins, Catarina Brás-Pereira, António Polónia, Maik Herbig, Clara Barreto, Oliver Otto, Joana Cardoso, José B Pereira-Leal, Jochen Guck, Joana Paredes, Florence Janody
Studies of the role of actin in tumour progression have highlighted its key contribution in cell softening associated with cell invasion. Here, using a human breast cell line with conditional Src induction, we demonstrate that cells undergo a stiffening state prior to acquiring malignant features. This state is characterized by the transient accumulation of stress fibres and upregulation of Ena/VASP-like (EVL). EVL, in turn, organizes stress fibres leading to transient cell stiffening, ERK-dependent cell proliferation, as well as enhancement of Src activation and progression towards a fully transformed state...
May 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28506909/the-selective-effect-of-glycyrrhizin-and-glycyrrhetinic-acid-on-topoisomerase-ii%C3%AE-and-apoptosis-in-combination-with-etoposide-on-triple-negative-breast-cancer-mda-mb-231-cells
#10
Yun Cai, Boxin Zhao, Qianying Liang, Yunqi Zhang, Jieying Cai, Guofeng Li
Triple negative breast cancer(TNBC) has generated growing interests due to its aggressive biologic behavior and absence of targeted therapy approach. Glycyrrhizin(GL) from licorice root and its metabolite, glycyrrhetinic acid(GA) have shown extensive bioactivities in clinic. Here, we demonstrate that GL and GA have contrary anti-cancer effect on TNBC MDA-MB-231 cells. Beside its inhibition of cell proliferation, GA at non-cytotoxic concentration showed synergistic effect in combination with anti-cancer drug, etoposide(VP-16)...
May 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28506194/the-use-of-systemic-therapies-to-prevent-progression-of-inflammatory-breast-cancer-which-targeted-therapies-to-add-on-cytotoxic-combinations
#11
Anthony Gonçalves, Audrey Monneur, Patrice Viens, François Bertucci
Inflammatory breast cancer is a rare but frequently fatal disease, essentially because of its high ability to develop distant metastases. Even though the prognosis of IBC was significantly improved by multimodal management, including the systematic use of cytotoxic-based induction, the prognosis remains largely dismal. Areas covered: This review presents the main achievements in the systemic treatment of IBC during the past 30 years. It focuses more specifically on recent results obtained with targeted therapies, including anti-HER2 and anti-angiogenic agents...
May 16, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28502728/technical-validation-of-a-next-generation-sequencing-assay-for-detecting-clinically-relevant-levels-of-breast-cancer-related-single-nucleotide-variants-and-copy-number-variants-using-simulated-cell-free-dna
#12
Xin Yang, Yuxing Chu, Rui Zhang, Yanxi Han, Lucheng Zhang, Yu Fu, Dan Li, Rongxue Peng, Dongdong Li, Jiansheng Ding, Ziyang Li, Meiru Zhao, Kuo Zhang, Tian Lu, Lang Yi, Qisheng Wu, Guigao Lin, Jiehong Xie, Tao Liu, Ling Yang, Xin Yi, Jinming Li
Next-generation sequencing (NGS) is commonly used in a clinical setting for diagnostic and prognostic testing of genetic mutations to select optimal targeted therapies. Herein, we describe the development of a custom NGS assay for detecting single-nucleotide variants (SNVs) and copy number variations (CNVs) in a panel of 51 genes related to breast cancer. We designed and implemented a validation strategy in accordance with principles and guidelines developed by the Next-Generation Sequencing: Standardization of Clinical Testing work group using artificial, cell-free DNA (cfDNA) with mutant fragments prepared in a simple, rapid, and cost-effective manner...
May 11, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28501705/doxorubicin-delivered-by-a-redox-responsive-dasatinib-containing-polymeric-prodrug-carrier-for-combination-therapy
#13
Jingjing Sun, Yanhua Liu, Yichao Chen, Wenchen Zhao, Qianyu Zhai, Sanjay Rathod, Yixian Huang, Suoqin Tang, Yong Tae Kwon, Christian Fernandez, Raman Venkataramanan, Song Li
Two novel prodrug polymers POEG-b-PSSDas (redox-sensitive) and POEG-b-PCCDas (redox-insensitive), which consist of poly(oligo(ethylene glycol) methacrylate) (POEG) hydrophilic blocks and dasatinib (DAS, an oncogenic tyrosine kinases inhibitor) conjugated hydrophobic blocks, were designed as dual-functional carriers for codelivery with doxorubicin (DOX). Both carriers retained antitumor activity of DAS and could form mixed micelles with DOX. Compared to POEG-b-PCCDas micelles, incorporation of disulfide linkage into POEG-b-PSSDas micelles facilitated efficient cleavage of DAS from prodrug micelles in tumor cells/tissues, leading to a higher level of anti-tumor activity in vitro and in vivo...
May 11, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28498399/dual-inhibition-of-igf1r-and-er-enhances-response-to-trastuzumab-in-her2-positive-breast-cancer-cells
#14
Martina S J McDermott, Alexandra Canonici, Laura Ivers, Brigid C Browne, Stephen F Madden, Neil A O'Brien, John Crown, Norma O'Donovan
Although HER2 targeted therapies have improved prognosis for HER2 positive breast cancer, HER2 positive cancers which co-express ER have poorer response rates to standard HER2 targeted therapies, combined with chemotherapy, than HER2 positive/ER negative breast cancer. Administration of hormone therapy concurrently with chemotherapy and HER2 targeted therapy is generally not recommended. Using publically available gene expression datasets we found that high expression of IGF1R is associated with shorter disease-free survival in patients whose tumors are ER positive and HER2 positive...
April 26, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28494449/effect-of-the-serum-inhibited-gene-si1-on-autophagy-and-apoptosis-in-mcf-7-breast-cancer-cells
#15
Yu Li, Yong Cui, Wenxue Wang, Mingxing Ma, Meizhang Li, Deyong Tan, Suiyun Chen
BACKGROUND/AIMS: The serum inhibited gene (Si1) was named according to its inhibited expression in response to serum exposure. Si1 has an important relationship with tumors. Autophagy and apoptosis are two types of cell death. However, there are few studies regarding the association between Si1 and autophagy, or apoptosis in tumors. In this, we investigated the effect of Si1 on the proliferation and cell cycle progression of MCF-7 cells and its influence on autophagy and apoptosis in MCF-7 cells...
April 26, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28493046/trastuzumab-uptake-and-its-relation-to-efficacy-in-an-animal-model-of-her2-positive-breast-cancer-brain-metastasis
#16
Gail D Lewis Phillips, Merry C Nishimura, Jennifer Arca Lacap, Samir Kharbanda, Elaine Mai, Janet Tien, Kimberly Malesky, Simon P Williams, Jan Marik, Heidi S Phillips
PURPOSE: The extent to which efficacy of the HER2 antibody Trastuzumab in brain metastases is limited by access of antibody to brain lesions remains a question of significant clinical importance. We investigated the uptake and distribution of trastuzumab in brain and mammary fat pad grafts of HER2-positive breast cancer to evaluate the relationship of these parameters to the anti-tumor activity of trastuzumab and trastuzumab emtansine (T-DM1). METHODS: Mouse transgenic breast tumor cells expressing human HER2 (Fo2-1282 or Fo5) were used to establish intracranial and orthotopic tumors...
May 10, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28491135/highlights-from-the-15th-st-gallen-international-breast-cancer-conference-15-18-march-2017-vienna-tailored-treatments-for-patients-with-early-breast-cancer
#17
Consuelo Morigi
The 15th St Gallen International Breast Cancer Conference was held in Vienna for the second time, from 15th-18th March 2017. 4000 people from 105 countries all over the world were invited to take part in the event. The real highlight of the conference was the last day with the International Consensus Session which was chaired by around 50 experts on breast cancer worldwide. With reference to data from scientific research, the consensus panel tried to offer guidelines for the management of breast cancer with the aim of providing patients with optimal treatment...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28488580/germline-mutations-in-pancreatic-cancer-and-potential-new-therapeutic-options
#18
REVIEW
Rille Pihlak, Juan W Valle, Mairéad G McNamara
Due to short-lived treatment responses in unresectable disease, pancreatic ductal adenocarcinoma (PDAC) continues to be one of the deadliest cancers. There is availability of new information about germline and sporadic mutations in the deoxyribonucleic acid (DNA) damage repair pathway in PDAC in recent decades and the expectation is that novel targeted therapies will thus be developed. A variety of germline mutations (BRCA2, BRCA1, PALB2, CDKN2A, ATM, TP53 and mismatch repair genes MLH1, MSH2, MSH6) have been reported in these patients with the highest prevalence being BRCA1/2...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28488143/methodology-of-phase-ii-clinical-trials-in-metastatic-elderly-breast-cancer-a-literature-review
#19
REVIEW
B Cabarrou, L Mourey, F Dalenc, L Balardy, D Kanoun, H Roché, J M Boher, M E Rougé-Bugat, Thomas Filleron
PURPOSE: As the incidence of invasive breast cancer will increase with age, the number of elderly patients with a diagnosis metastatic breast cancer will also rise. But the use of cytotoxic drugs in elderly metastatic breast cancer patients is not systematic and is dreaded by medical oncologists. The need for prospective oncologic data from this population seems increasingly obvious. The main objective of this review is to investigate design and characteristics of phase II trials that assess activity and feasibility of chemotherapies in elderly advanced/metastatic breast cancer patients...
May 9, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28487467/overall-survival-and-clinical-characteristics-of-brca-associated-cholangiocarcinoma-a-multicenter-retrospective-study
#20
Talia Golan, Maria Raitses-Gurevich, Robin K Kelley, Andrea G Bocobo, Ayelet Borgida, Rachna T Shroff, Spring Holter, Steven Gallinger, Daniel H Ahn, Dan Aderka, Jain Apurva, Tanois Bekaii-Saab, Eitan Friedman, Milind Javle
BACKGROUND: Biliary tract malignancies, in particular cholangiocarcinomas (CCA), are rare tumors that carry a poor prognosis. BRCA2 mutation carriers have an increased risk of developing CCA with a reported relative risk of ∼5 according to the Breast Cancer Linkage Consortium. In addition to this risk, there are potential therapeutic implications in those harboring somatic and/or germline (GL) BRCA mutations. Therefore, it is important to define the clinical characteristics of GL/somatic BRCA1/2 variants in CCA patients...
May 9, 2017: Oncologist
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