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ERBB3 AND cancer

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https://www.readbyqxmd.com/read/28421882/inhibition-of-her3-activation-and-tumor-growth-with-a-human-antibody-binding-to-a-conserved-epitope-formed-by-domain-iii-and-iv
#1
Lisa C Schmitt, Alexander Rau, Oliver Seifert, Jonas Honer, Meike Hutt, Simone Schmid, Jonas Zantow, Michael Hust, Stefan Dübel, Monilola A Olayioye, Roland E Kontermann
Human epidermal growth factor receptor 3 (HER3, also known as ErbB3) has emerged as relevant target for antibody-mediated tumor therapy. Here, we describe a novel human antibody, IgG 3-43, recognizing a unique epitope formed by domain III and parts of domain IV of the extracellular region of HER3, conserved between HER3 and mouse ErbB3. An affinity of 11 nM was determined for the monovalent interaction. In the IgG format, the antibody bound recombinant bivalent HER3 with subnanomolar affinity (KD = 220 pM) and HER3-expressing tumor cells with EC50 values in the low picomolar range (27 - 83 pM)...
April 19, 2017: MAbs
https://www.readbyqxmd.com/read/28404378/axl-molecular-targeting-counteracts-aggressiveness-but-not-platinum-resistance-of-ovarian-carcinoma-cells
#2
Cristina Corno, Laura Gatti, Noemi Arrighetti, Nives Carenini, Nadia Zaffaroni, Cinzia Lanzi, Paola Perego
Ovarian carcinoma, the most common gynecological cancer, is characterized by high lethality mainly due to late diagnosis and treatment failure. The efficacy of platinum drug-based therapy in the disease is limited by the occurrence of drug resistance, a phenomenon often associated with increased metastatic potential. Because the Tyr-kinase receptor Axl can be deregulated in ovarian carcinoma and plays a pro-metastatic/anti-apoptotic role, the aim of this study was to examine if Axl inhibition modulates drug resistance and aggressive features of ovarian carcinoma cells, using various pairs of cisplatin-sensitive and -resistant cell lines...
April 9, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28399526/expression-of-the-erbb-family-of-ligands-and-receptors-in-gastric-cancer
#3
Sun-Ju Byeon, Hye Seung Lee, Min-A Kim, Byung Lan Lee, Woo Ho Kim
OBJECTIVE: Gastric cancer (GC) is the second most common cancer and the third leading cause of cancer-related death in Korea. Alterations in the ERBB (homology to the erythroblastoma viral gene product, v-erbB) receptor family and ERBB-related signaling pathways are frequently observed in GC. However, the roles of the ERBB receptors and their ligands in GC are not well established. METHODS: We evaluated the expression levels of various ERBB receptor ligands (i.e...
April 12, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28369073/her2-signaling-regulates-her2-localization-and-membrane-retention
#4
Jaekwang Jeong, Wonnam Kim, Lark Kyun Kim, Joshua VanHouten, John J Wysolmerski
ErbB2/HER2/Neu is a receptor tyrosine kinase that is overexpressed in 25-30% of human breast cancers, usually associated with amplification of the ERBB2 gene. HER2 has no recognized ligands and heterodimers between HER2 and EGFR (ErbB1/HER1) or HER2 and ErbB3/HER3 are important in breast cancer. Unlike other ErbB family members, HER2 is resistant to internalization and degradation, and remains at the cell surface to signal for prolonged periods after it is activated. Although the mechanisms underlying retention of HER2 at the cell surface are not fully understood, prior studies have shown that, in order to avoid internalization, HER2 must interact with the chaperone, HSP90, and the calcium pump, PMCA2, within specific plasma membrane domains that protrude from the cell surface...
2017: PloS One
https://www.readbyqxmd.com/read/28350117/reduced-expression-of-mir%C3%A2-205%C3%A2-5p-promotes-apoptosis-and-inhibits-proliferation-and-invasion-in-lung-cancer-a549-cells-by-upregulation-of-zeb2-and-downregulation-of-erbb3
#5
Min Jiang, Ting Zhong, Wei Zhang, Zuke Xiao, Guozhu Hu, Hong Zhou, Haibin Kuang
Previous studies have demonstrated that microRNA (miR)-205-5p expression is significantly increased in non‑small cell lung cancer tissues and is associated with tumor differentiation grade. The aim of the present study was to explore the effects of miR‑205‑5p on viability, apoptosis and invasion of lung cancer A549 cells. The hsa‑miR‑205‑5p small interfering RNA (siRNA) inhibitor was transfected into A549 cells and expression of miR‑205‑5p was detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR)...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28338617/egfr-family-members-regulation-of-autophagy-is-at-a-crossroads-of-cell-survival-and-death-in-cancer
#6
REVIEW
Elizabeth Henson, Yongqiang Chen, Spencer Gibson
The epidermal growth factor receptor (EGFR) signaling pathways are altered in many cancers contributing to increased cell survival. These alterations are caused mainly through increased expression or mutation of EGFR family members EGFR, ErbB2, ErbB3, and ErbB4. These receptors have been successfully targeted for cancer therapy. Specifically, a monoclonal antibody against ErbB2, trastuzumab, and a tyrosine kinase inhibitor against EGFR, gefitinib, have improved the survival of breast and lung cancer patients...
March 24, 2017: Cancers
https://www.readbyqxmd.com/read/28294470/exome-sequencing-deciphers-a-germline-met-mutation-in-familial-epidermal-growth-factor-receptor-mutant-lung-cancer
#7
Naoki Tode, Toshiaki Kikuchi, Tomohiro Sakakibara, Taizou Hirano, Akira Inoue, Shinya Ohkouchi, Tsutomu Tamada, Tatsuma Okazaki, Akira Koarai, Hisatoshi Sugiura, Tetsuya Niihori, Yoko Aoki, Keiko Nakayama, Kunio Matsumoto, Yoichi Matsubara, Masayuki Yamamoto, Akira Watanabe, Toshihiro Nukiwa, Masakazu Ichinose
Lung cancer accompanied by somatic activating mutations in the epidermal growth factor receptor (EGFR) gene, which is associated with a significant clinical response to the targeted therapy, is frequently found in never-smoking Asian women with adenocarcinoma. Although this implies genetic factors underlying the carcinogenesis, the etiology remains unclear. To gain insight into the pathogenic mechanisms, we sequenced the exomes in the peripheral-blood DNA from six siblings, four affected and two unaffected siblings, of a kindred with familial EGFR-mutant lung adenocarcinoma...
March 13, 2017: Cancer Science
https://www.readbyqxmd.com/read/28286209/esophageal-adenocarcinoma-cells-and-xenograft-tumors-exposed-to-erb-b2-receptor-tyrosine-kinase-2-and-3-inhibitors-activate-transforming-growth-factor-beta-signaling-which-induces-epithelial-to-mesenchymal-transition
#8
Eva A Ebbing, Anne Steins, Evelyn Fessler, Phylicia Stathi, Willem Joost Lesterhuis, Kausilia K Krishnadath, Louis Vermeulen, Jan Paul Medema, Maarten F Bijlsma, Hanneke W M van Laarhoven
BACKGROUND & AIMS: Drugs that inhibit the erb-b2 receptor tyrosine kinase 2 (ERBB2 or HER2) are the standard treatment of patients with different types of cancer, including HER2-overexpressing gastroesophageal tumors. Unfortunately, cancer cells become resistant to these drugs, so overall these drugs provide little benefit to patients with these tumors. We investigated mechanisms that mediate resistance of esophageal adenocarcinoma (EAC) cells and patient-derived xenograft (PDX) tumors to ERBB inhibitors...
March 9, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28285962/the-erk-mapk-pathway-is-overexpressed-and-activated-in-gallbladder-cancer
#9
Kurt Buchegger, Ramón Silva, Jaime López, Carmen Ili, Juan Carlos Araya, Pamela Leal, Priscilla Brebi, Ismael Riquelme, Juan Carlos Roa
Gallbladder cancer (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. Molecular profiling has revealed that the deregulation in the ERK/MAPK signaling pathway plays a crucial role in many disease and malignancies, including GBC. The aim of this study was to measure the expression of ERK1/2 and p-ERK1/2 in a population with high GBC-related mortality, such as the Chilean population, and characterize the protein expression of this ERK/MAPK pathway in seven GBC cell lines. Immunohistochemistry (IHC) for ERK1/2 and p-ERK1/2 was performed in 123 GBC tissues and 37 chronic cholecystitis (CC) tissues...
February 24, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28223167/intracavitary-t4-immunotherapy-of-malignant-mesothelioma-using-pan-erbb-re-targeted-car-t-cells
#10
Astero Klampatsa, Daniela Y Achkova, David M Davies, Ana C Parente-Pereira, Natalie Woodman, James Rosekilly, Georgina Osborne, Thivyan Thayaparan, Andrea Bille, Michael Sheaf, James F Spicer, Juliet King, John Maher
Malignant mesothelioma remains an incurable cancer. We demonstrated that mesotheliomas expressed EGFR (79.2%), ErbB4 (49.0%) and HER2 (6.3%), but lacked ErbB3. At least one ErbB family member was expressed in 88% of tumors. To exploit ErbB dysregulation in this disease, patient T-cells were engineered by retroviral transduction to express a panErbB-targeted chimeric antigen receptor (CAR), co-expressed with a chimeric cytokine receptor that allows interleukin (IL)-4 mediated CAR T-cell proliferation. This combination is referred to as T4 immunotherapy...
February 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28209614/distinct-interactions-of-ebp1-isoforms-with-fbxw7-elicits-different-functions-in-cancer
#11
Yuli Wang, Pengju Zhang, Yunshan Wang, Panpan Zhan, Chunyan Liu, Jian-Hua Mao, Guangwei Wei
The ErbB3 receptor-binding protein EBP1 encodes two alternatively spliced isoforms P48 and P42. While there is evidence of differential roles for these isoforms in tumorigenesis, little is known about their underlying mechanisms. Here, we demonstrate that EBP1 isoforms interact with the SCF-type ubiquitin ligase FBXW7 in distinct ways to exert opposing roles in tumorigenesis. EBP1 P48 bound to the WD domain of FBXW7 as an oncogenic substrate of FBXW7. EBP1 P48 binding sequestered FBXW7α to the cytosol, modulating its role in protein degradation and attenuating its tumor suppressor function...
April 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28197371/prophylactic-vaccination-targeting-erbb3-decreases-polyp-burden-in-a-mouse-model-of-human-colorectal-cancer
#12
David J Bautz, Ang T Sherpa, David W Threadgill
Prophylactic vaccination is typically utilized for the prevention of communicable diseases such as measles and influenza but, with the exception of vaccines to prevent cervical cancer, is not widely used as a means of preventing or reducing the incidence of cancer. Here, we utilize a peptide-based immunotherapeutic approach targeting ERBB3, a pseudo-kinase member of the EGFR/ERBB family of receptor tyrosine kinases, as a means of preventing occurrence of colon polyps. Administration of the peptide resulted in a significant decrease in the development of intestinal polyps in C57BL/6J-Apc(Min) mice, a model of familial adenomatous polyposis (FAP)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28174229/effects-of-erbb2-overexpression-on-the-proteome-and-erbb-ligand-specific-phosphosignaling-in-mammary-luminal-epithelial-cells
#13
Jenny Worthington, Georgia Spain, John F Timms
Most breast cancers arise from luminal epithelial cells, and 25-30% of these tumors overexpress the ErbB2/HER2 receptor that correlates with disease progression and poor prognosis. The mechanisms of ErbB2 signaling and the effects of its overexpression are not fully understood. Herein, stable isotope labeling by amino acids in cell culture (SILAC), expression profiling, and phosphopeptide enrichment of a relevant, non-transformed, and immortalized human mammary luminal epithelial cell model were used to profile ErbB2-dependent differences in protein expression and phosphorylation events triggered via EGF receptor (EGF treatment) and ErbB3 (HRG1β treatment) in the context of ErbB2 overexpression...
April 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28112728/integrated-genomic-and-molecular-characterization-of-cervical-cancer
#14
(no author information available yet)
Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Here we report the extensive molecular characterization of 228 primary cervical cancers, one of the largest comprehensive genomic studies of cervical cancer to date. We observed notable APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered amplifications in immune targets CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2), and the BCAR4 long non-coding RNA, which has been associated with response to lapatinib...
March 16, 2017: Nature
https://www.readbyqxmd.com/read/28060735/the-natural-compound-fucoidan-from-new-zealand-undaria-pinnatifida-synergizes-with-the-erbb-inhibitor-lapatinib-enhancing-melanoma-growth-inhibition
#15
Varsha Thakur, Jun Lu, Giuseppe Roscilli, Luigi Aurisicchio, Manuela Cappelletti, Emiliano Pavoni, William Lindsey White, Barbara Bedogni
Melanoma remains one of the most aggressive and therapy-resistant cancers. Finding new treatments to improve patient outcomes is an ongoing effort. We previously demonstrated that melanoma relies on the activation of ERBB signaling, specifically of the ERBB3/ERBB2 cascade. Here we show that melanoma tumor growth is inhibited by 60% over controls when treated with lapatinib, a clinically approved inhibitor of ERBB2/EGFR. Importantly, tumor growth is further inhibited to 85% when the natural compound fucoidan from New Zealand U...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28050146/personalized-oncogenomics-in-the-management-of-gastrointestinal-carcinomas-early-experiences-from-a-pilot-study
#16
B S Sheffield, B Tessier-Cloutier, H Li-Chang, Y Shen, E Pleasance, K Kasaian, Y Li, S J M Jones, H J Lim, D J Renouf, D G Huntsman, S Yip, J Laskin, M Marra, D F Schaeffer
BACKGROUND: Gastrointestinal carcinomas are genomically complex cancers that are lethal in the metastatic setting. Whole-genome and transcriptome sequencing allow for the simultaneous characterization of multiple oncogenic pathways. METHODS: We report 3 cases of metastatic gastrointestinal carcinoma in patients enrolled in the Personalized Onco-Genomics program at the BC Cancer Agency. Real-time genomic profiling was combined with clinical expertise to diagnose a carcinoma of unknown primary, to explore treatment response to bevacizumab in a colorectal cancer, and to characterize an appendiceal adenocarcinoma...
December 2016: Current Oncology
https://www.readbyqxmd.com/read/28036286/her3-and-linc00052-interplay-promotes-tumor-growth-in-breast-cancer
#17
Ahmad Salameh, Xuejun Fan, Byung-Kwon Choi, Shu Zhang, Ningyan Zhang, Zhiqiang An
Here we report that the lncRNA LINC00052 expression correlates positively with HER3/ErbB3 levels in breast cancer cells. Gene silencing of LINC00052 diminished both LINC00052 and HER3 expression and reduced cancer cell growth in vitro and in vivo. LINC00052 overexpression promoted cancer cell growth in vitro and in vivo and increased HER3-mediated downstream signaling. Importantly, neutralization of HER3 signaling with HER3 targeting monoclonal antibodies blocked LINC00052 mediated cancer cell proliferation in vitro and tumor growth in vivo, suggesting LINC00052 promoting cancer growth through HER3 signaling...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28004068/-up-regulation-of-erbb3-binding-protein-1-inhibits-the-growth-of-esophageal-carcinoma-cells
#18
Hao Jiang, Dong-Ping Liu, Dong Xie, Dong-Zhi Wei
The objective of this study was to investigate the role of ErbB3-binding protein 1 (Ebp1) in the growth of esophageal squamous cell carcinoma (ESCC) cells and the underlying mechanism. Eca109 and KYSE150 cells were transfected with lentiviral vector carrying Ebp1 gene. The mRNA levels of Ebp1 in esophageal cancer tissues and paired adjacent normal tissues were examined by real-time PCR. The growth and viability of esophageal carcinoma cells were assessed using MTT and crystal violet assays, respectively. Clone-forming abilities of Eca109 and KYSE150 cells were analyzed by soft agar assay...
December 25, 2016: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/27998236/randomized-phase-ii-trial-of-seribantumab-in-combination-with-paclitaxel-in-patients-with-advanced-platinum-resistant-or-refractory-ovarian-cancer
#19
Joyce F Liu, Isabelle Ray-Coquard, Frederic Selle, Andrés M Poveda, David Cibula, Hal Hirte, Felix Hilpert, Francesco Raspagliesi, Laurence Gladieff, Philipp Harter, Salvatore Siena, Josep Maria Del Campo, Isabelle Tabah-Fisch, Joseph Pearlberg, Victor Moyo, Kaveh Riahi, Rachel Nering, William Kubasek, Bambang Adiwijaya, Akos Czibere, R Wendel Naumann, Robert L Coleman, Ignace Vergote, Gavin MacBeath, Eric Pujade-Lauraine
Purpose Seribantumab is a fully human immunoglobulin G2 monoclonal antibody that binds to human epidermal growth factor receptor (HER) 3 (ErbB3), blocking heregulin (HRG) -mediated ErbB3 signaling and inducing ErbB3 receptor downregulation. This open-label randomized phase II study evaluated progression-free survival (PFS) with seribantumab in combination with once-per-week paclitaxel compared with paclitaxel alone in patients with platinum-resistant or -refractory ovarian cancer. A key secondary objective was to determine if any of five prespecified biomarkers predicted benefit from seribantumab...
December 20, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27906435/down-regulation-of-microrna-143-is-associated-with-colorectal-cancer-progression
#20
J-W Bai, H-Z Xue, C Zhang
OBJECTIVE: Colorectal cancer (CRC) is one of the most prevalent carcinomas worldwide. Tumor metastasis and recurrence are leading causes of CRC-related deaths. Given the role of microRNA (miRNA) in CRC invasion and metastasis, we explored the association between miRNA-143 expression and clinicopathologic characteristics in CRC, as well as the effects of miRNA-143 on CRC cell invasion in vitro. MATERIALS AND METHODS: Quantitative real-time PCR was conducted to assess the expression of miR-143 in tissue specimens and cell lines...
November 2016: European Review for Medical and Pharmacological Sciences
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