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https://www.readbyqxmd.com/read/28797930/%C3%AE-tocotrienol-induced-disruption-of-lipid-rafts-in-human-breast-cancer-cells-is-associated-with-a-reduction-in-exosome-heregulin-content
#1
Osama A Alawin, Rayan A Ahmed, Venkateshwararao Dronamraju, Karen P Briski, Paul W Sylvester
Overexpression of heregulin, a potent ligand that activates HER3 and HER4 receptors, plays a significant role in the development of chemotherapy resistance in breast cancer patients. Exosomes released from cancer cells are small vesicles originating from the outward budding of lipid rafts that carry various mitogenic proteins that then act locally in an autocrine/paracrine manner to stimulate cancer cell growth. Since the anticancer activity of γ-tocotrienol has been shown to be mediated in part through the disruption of lipid rafts, studies were conducted to determine the effect of γ-tocotrienol on exosomes mitogenic biopotency...
July 10, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28791648/assessment-of-specificity-of-an-adenovirus-targeted-to-her3-4
#2
Sheena H MacLeod, Kyle G Potts, Shyambabu Chaurasiya, Mary M Hitt
Gene therapy with viral vectors, such as adenovirus (Ad), targeted to the human epidermal growth factor receptors 3 and 4 (HER3/4) are potentially useful for cancer therapy. Testing the expression of a reporter gene from these viruses in target cells is essential to determine functionality of the targeted virus. A competition assay with a relevant ligand (heregulin, HRG) can provide convincing evidence that blocking binding to the HER3/4 receptor results in decreased reporter gene expression. Labeling individual viruses with a fluorescent molecule allows examination of the targeted virus in specific steps in the infection...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28791631/erbb-receptors-and-cancer
#3
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
https://www.readbyqxmd.com/read/28733706/phage-display-selection-in-vitro-characterization-and-correlative-pet-imaging-of-a-novel-her3-peptide
#4
Benjamin M Larimer, Nicholas Phelan, Eric Wehrenberg-Klee, Umar Mahmood
PURPOSE: HER3 (ERBB3) is a receptor tyrosine kinase that is implicated in treatment resistance across multiple cancers, including those of the breast, lung, and prostate. Overexpression of HER3 following targeted therapy can occur rapidly and heterogeneously both within a single lesion and across sites of metastasis, making protein quantification by biopsy highly challenging. A global, non-invasive methodology such as positron emission tomography (PET) imaging can permit serial quantification of HER3, providing a useful approach to monitor HER3 expression across the entire tumor burden both prior to and following treatment...
July 21, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28733442/-89-zr-lumretuzumab-pet-imaging-before-and-during-her3-antibody-lumretuzumab-treatment-in-patients-with-solid-tumors
#5
Frederike Bensch, Laetitia E Lamberts, Michaël M Smeenk, Annelies Jorritsma-Smit, Marjolijn N Lub-de Hooge, Anton G T Terwisscha van Scheltinga, Johan R de Jong, Jourik A Gietema, Carolina P Schröder, Marlene Thomas, Wolfgang Jacob, Keelara Abiraj, Celine Adessi, Georgina Meneses-Lorente, Ian James, Martin Weisser, Adrienne H Brouwers, Elisabeth G de Vries
Purpose: We evaluated biodistribution and tumor targeting of (89)Zr-lumretuzumab before and during treatment with lumretuzumab, a human epidermal growth factor receptor 3 (HER3)-targeting monoclonal antibody. <p>Experimental design: 20 patients with histologically confirmed HER3-expressing tumors received (89)Zr-lumretuzumab and underwent Positron Emission Tomography (PET). In Part A, (89)Zr-lumretuzumab was given with additional, escalating doses of unlabeled lumretuzumab and scans were performed 2, 4 and 7 days postinjection to determine optimal imaging conditions...
July 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28732202/retraction-notice-to-an-atp-competitive-inhibitor-modulates-the-allosteric-function-of-the-her3-pseudokinase
#6
Peter Littlefield, Mark M Moasser, Natalia Jura
No abstract text is available yet for this article.
July 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28730475/characterization-of-ligand-binding-to-pseudokinases-using-a-thermal-shift-assay
#7
Isabelle S Lucet, James M Murphy
The protocol herein describes a robust and proven method for the measurement of pseudokinase-ligand interaction using a fluorescence-based thermal shift assay (TSA). Pseudokinases are kinase-like proteins that have recently emerged as crucial regulatory modules of signal transduction pathways and may well represent a novel class of drug targets. However, unlike kinases, the regulatory activity of pseudokinases is mainly conferred through protein-protein interactions. Understanding the mechanisms that underlie pseudokinase conformational changes through ligand binding and how such conformational changes can tune signaling pathways is a necessary step to unravel their biological functions...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28725482/systems-biology-driving-drug-development-from-design-to-the-clinical-testing-of-the-anti-erbb3-antibody-seribantumab-mm-121
#8
REVIEW
Birgit Schoeberl, Art Kudla, Kristina Masson, Ashish Kalra, Michael Curley, Gregory Finn, Emily Pace, Brian Harms, Jaeyeon Kim, Jeff Kearns, Aaron Fulgham, Olga Burenkova, Viara Grantcharova, Defne Yarar, Violette Paragas, Jonathan Fitzgerald, Marisa Wainszelbaum, Kip West, Sara Mathews, Rachel Nering, Bambang Adiwijaya, Gabriela Garcia, Bill Kubasek, Victor Moyo, Akos Czibere, Ulrik B Nielsen, Gavin MacBeath
The ErbB family of receptor tyrosine kinases comprises four members: epidermal growth factor receptor (EGFR/ErbB1), human EGFR 2 (HER2/ErbB2), ErbB3/HER3, and ErbB4/HER4. The first two members of this family, EGFR and HER2, have been implicated in tumorigenesis and cancer progression for several decades, and numerous drugs have now been approved that target these two proteins. Less attention, however, has been paid to the role of this family in mediating cancer cell survival and drug tolerance. To better understand the complex signal transduction network triggered by the ErbB receptor family, we built a computational model that quantitatively captures the dynamics of ErbB signaling...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28723928/erbb-activation-signatures-as-potential-biomarkers-for-anti-erbb3-treatment-in-hnscc
#9
Diego Alvarado, Gwenda F Ligon, Jay S Lillquist, Scott B Seibel, Gerald Wallweber, Veronique M Neumeister, David L Rimm, Gerald McMahon, Theresa M LaVallee
Head and neck squamous cell carcinoma (HNSCC) accounts for 3-5% of all tumor types and remains an unmet medical need with only two targeted therapies approved to date. ErbB3 (HER3), the kinase-impaired member of the EGFR/ErbB family, has been implicated as a disease driver in a number of solid tumors, including a subset of HNSCC. Here we show that the molecular components required for ErbB3 activation, including its ligand neuregulin-1 (NRG1), are highly prevalent in HNSCC and that HER2, but not EGFR, is the major activating ErbB3 kinase partner...
2017: PloS One
https://www.readbyqxmd.com/read/28708592/a-peptidomimetic-with-a-chiral-switch-is-an-inhibitor-of-epidermal-growth-factor-receptor-heterodimerization
#10
Shanthi P Kanthala, Yong-Yu Liu, Sitanshu Singh, Rushikesh Sable, Sandeep Pallerla, Seetharama D Jois
Among different types of EGFR dimers, EGFR-HER2 and HER2-HER3 are well known in different types of cancers. Targeting dimerization of EGFR will have a significant impact on cancer therapies. A symmetric peptidomimetic was designed to inhibit the protein-protein interaction of EGFR. The peptidomimetic (Cyclo(1,10)PpR (R) Anapa-FDDF-(R)-Anapa)R, compound 18) was shown to exhibit antiproliferative activity with an IC50 of 194 nM in HER2-expressing breast cancer cell lines and 18 nM in lung cancer cell lines. The peptidomimetic has a Pro-Pro sequence in the structure to stabilize the β-turn and a β-amino acid, amino napthyl propionic acid...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28680745/vaccination-targeting-human-her3-alters-the-phenotype-of-infiltrating-t-cells-and-responses-to-immune-checkpoint-inhibition
#11
Takuya Osada, Michael A Morse, Amy Hobeika, Marcio A Diniz, William R Gwin, Zachary Hartman, Junping Wei, Hongtao Guo, Xiao-Yi Yang, Cong-Xiao Liu, Kensuke Kaneko, Gloria Broadwater, H Kim Lyerly
Expression of human epidermal growth factor family member 3 (HER3), a critical heterodimerization partner with EGFR and HER2, promotes more aggressive biology in breast and other epithelial malignancies. As such, inhibiting HER3 could have broad applicability to the treatment of EGFR- and HER2-driven tumors. Although lack of a functional kinase domain limits the use of receptor tyrosine kinase inhibitors, HER3 contains antigenic targets for T cells and antibodies. Using novel human HER3 transgenic mouse models of breast cancer, we demonstrate that immunization with recombinant adenoviral vectors encoding full length human HER3 (Ad-HER3-FL) induces HER3-specific T cells and antibodies, alters the T cell infiltrate in tumors, and influences responses to immune checkpoint inhibitions...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28671339/role-of-erbb-her-family-of-receptor-tyrosine-kinases-in-cholangiocyte-biology
#12
REVIEW
Anna Pellat, Javier Vaquero, Laura Fouassier
The ErbB/HER family comprises four distinct tyrosine kinase receptors, EGFR/ErbB1/HER1, ErbB2/HER2, ErbB3/HER3 and ErbB4/HER4, which trigger intracellular signals at the origin of essential cellular functions including differentiation, proliferation, survival and migration. Epithelial cells, named cholangiocytes, that line intrahepatic and extrahepatic bile ducts, contribute substantially to biliary secretory functions and bile transport. Although ErbB receptors have been widely studied in cholangiocarcinoma (CCA), a malignancy of the biliary tract, knowledge of these receptors in biliary epithelium physiology and in non-malignant cholangiopathies is far from completed...
July 3, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28656214/her2-regulates-cancer-stem-like-cell-phenotype-in-alk-translocated-nsclc
#13
Tiia Honkanen, Emmi Wilenius, Peppi Koivunen, Jussi P Koivunen
We have previously shown that cancer stem-like cells (CSLCs) can mediate therapy resistance in ALK translocated lung cancers. HER2 has been linked to CSLCs in breast cancers and, therefore, we wanted to assess whether HER2 has a role in CSLCs in ALK translocated cancers. ALK translocated cell lines, H3122 and H2228, with variable sensitivity to ALK inhibition were used in the study. HER2 overexpression or knockdown was induced by retro- or lentiviral infections and cells were treated with pharmacological agents targeting HER2 and ALK signaling...
June 21, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28653892/specific-antibodies-and-sensitive-immunoassays-for-the-human-epidermal-growth-factor-receptors-her2-her3-and-her4
#14
Marianne Nordlund Broughton, Arne Westgaard, Elisabeth Paus, Miriam Øijordsbakken, Karoline J Henanger, Bjørn Naume, Trine Bjøro
The use of trastuzumab in patients with breast cancer that overexpresses human epidermal growth factor receptor 2 has significantly improved treatment outcomes. However, a substantial proportion of this patient group still experiences progression of the disease after receiving the drug. Evaluation of the changes in expression of the human epidermal growth factor receptors could be of interest. Monoclonal antibodies against the extracellular domain of the human growth factor receptors, 2, 3, and 4, have been raised, and specific and sensitive immunoassays have been established...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28646172/dacomitinib-a-pan-inhibitor-of-erbb-receptors-suppresses-growth-and-invasive-capacity-of-chemoresistant-ovarian-carcinoma-cells
#15
Majid Momeny, Ghazaleh Zarrinrad, Farima Moghaddaskho, Arash Poursheikhani, Ghazaleh Sankanian, Azam Zaghal, Shahab Mirshahvaladi, Fatemeh Esmaeili, Haniyeh Eyvani, Farinaz Barghi, Zahra Sabourinejad, Zivar Alishahi, Hassan Yousefi, Reza Ghasemi, Leila Dardaei, Davood Bashash, Bahram Chahardouli, Ahmad R Dehpour, Javad Tavakkoly-Bazzaz, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy worldwide. Development of chemoresistance and peritoneal dissemination of EOC cells are the major reasons for low survival rate. Targeting signal transduction pathways which promote therapy resistance and metastatic dissemination is the key to successful treatment. Members of the ErbB family of receptors are over-expressed in EOC and play key roles in chemoresistance and invasiveness. Despite this, single-targeted ErbB inhibitors have demonstrated limited activity in chemoresistant EOC...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645115/a-comprehensive-review-of-heregulins-her3-and-her4-as-potential-therapeutic-targets-in-cancer
#16
REVIEW
Jose Mauricio Mota, Katharine Ann Collier, Ricardo Lima Barros Costa, Timothy Taxter, Aparna Kalyan, Caio A Leite, Young Kwang Chae, Francis J Giles, Benedito A Carneiro
Heregulins (HRGs) bind to the receptors HER3 or HER4, induce receptor dimerization, and trigger downstream signaling that leads to tumor progression and resistance to targeted therapies. Increased expression of HRGs has been associated with worse clinical prognosis; therefore, attempts to block HRG-dependent tumor growth have been pursued. This manuscript summarizes the function and signaling of HRGs and review the preclinical evidence of its involvement in carcinogenesis, prognosis, and treatment resistance in several malignancies such as colorectal cancer, non-small cell lung cancer, ovarian cancer, and breast cancer...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28615452/interplay-of-the-iron-regulated-metastasis-suppressor-ndrg1-with-epidermal-growth-factor-receptor-egfr-and-oncogenic-signaling
#17
REVIEW
Sharleen V Menezes, Sumit Sahni, Zaklina Kovacevic, Des R Richardson
The iron-regulated metastasis suppressor N-myc downstream-regulated gene 1 (NDRG1) has been shown to inhibit numerous oncogenic signaling pathways in cancer cells. Recent findings have demonstrated that NDRG1 inhibits the ErbB family of receptors, which function as key inducers of carcinogenesis. NDRG1 attenuates ErbB signaling by inhibiting formation of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2) and HER2/HER3 heterodimers and by down-regulating EGFR via a mechanism involving its degradation...
August 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28610664/retraction-notice-to-silencing-egfr-her3-signaling-with-a-novel-anti-egfr-domain-ii-iv-antibody-cancer-lett-357-2015-374-383
#18
Shi Hu, Haibin Dai, Tiancheng Zhang, Wenyan Fu, Sandra D Berezov, Cheng Chen, Daniel Jorissen, Hiroaki Takeda, Augus N Bethune
No abstract text is available yet for this article.
August 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28600476/phase-ib-study-of-lumretuzumab-plus-cetuximab-or-erlotinib-in-solid-tumor-patients-and-evaluation-of-her3-and-heregulin-as-potential-biomarkers-of-clinical-activity
#19
Didier Meulendijks, Wolfgang Jacob, Emile E Voest, Morten Mau-Sørensen, Maria Martinez-Garcia, Alvaro Taus, Tania Fleitas, Andres Cervantes, Martijn Lolkema, Marlies Hg Langenberg, Maja J A de Jonge, Stefan Sleijfer, Ji-Youn Han, Antonio Calles, Enriqueta Felip, Sang-We Kim, Jan H M Schellens, Sabine Wilson, Marlene Thomas, Maurizio Ceppi, Georgina Meneses-Lorente, Ian James, Suzana Vega Harring, Rajiv Dua, Maitram Nguyen, Lori Steiner, Celine Adessi, Francesca Michielin, Birgit Bossenmaier, Martin Weisser, Ulrik Lassen
<br /> <p>This study investigated the safety, clinical activity and target-associated biomarkers of lumretuzumab, a humanized, glycoengineered, anti-HER3 monoclonal antibody (mAb), in combination with the EGFR-blocking agents erlotinib or cetuximab in patients with advanced HER3-positive carcinomas.</p> <br />Experimental Design: <br /> <p>The study included two parts: dose escalation and dose extension phases with lumretuzumab in combination with either cetuximab or erlotinib, respectively...
June 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28592615/a-phase-ib-dose-escalation-study-of-the-safety-tolerability-and-pharmacokinetics-of-cobimetinib-and-duligotuzumab-in-patients-with-previously-treated-locally-advanced-or-metastatic-cancers-with-mutant-kras
#20
Christopher H Lieu, Manuel Hidalgo, Jordan D Berlin, Andrew H Ko, Andres Cervantes, Patricia LoRusso, David E Gerber, J Paul Eder, S Gail Eckhardt, Amy V Kapp, Amy Tsuhako, Bruce McCall, Andrea Pirzkall, Anne Uyei, Josep Tabernero
LESSONS LEARNED: Cobimetinib and duligotuzumab were well tolerated as single agents and in combination with other agents.The cobimetinib and duligotuzumab combination was associated with increased toxicity, most notably gastrointestinal, and limited efficacy in the patient population tested. BACKGROUND: KRAS-mutant tumors possess abnormal mitogen-activated protein kinases (MAPK) pathway signaling, leading to dysregulated cell proliferation. Cobimetinib blocks MAPK signaling...
June 7, 2017: Oncologist
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