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https://www.readbyqxmd.com/read/28919583/polyclonal-antibody-against-different-extracellular-subdomains-of-her2-induces-tumor-growth-inhibition-in-vitro
#1
Reza Hosseini Ghatar, Tahereh Soltantoyeh, Motahareh Bahadori, Jalal Khoshnoodi, Forough Golsaz Shirazi, Mahmood Jeddi Tehrani, Mohammad Mehdi Amiri, Fazel Shokri
BACKGROUND: Human epidermal growth factor receptor 2 (HER2) has a crucial role in several malignancies. The extracellular domain of HER2 (HER2-ECD) has been extensively employed as an important target in passive and active immunotherapy. Isolated recombinant prokaryotic HER2-ECD subdomains were previously found to be ineffective in inducing anti-tumor antibody response. OBJECTIVE: To employ recombinant eukaryotic HER2-ECD subdomains to raise anti-HER2 antibodies and determine their anti-tumor activity in vitro...
September 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/28915642/a-retrospective-multicentric-observational-study-of-trastuzumab-emtansine-in-her2-positive-metastatic-breast-cancer-a-real-world-experience
#2
Patrizia Vici, Laura Pizzuti, Andrea Michelotti, Isabella Sperduti, Clara Natoli, Lucia Mentuccia, Luigi Di Lauro, Domenico Sergi, Paolo Marchetti, Daniele Santini, Emanuela Magnolfi, Laura Iezzi, Luca Moscetti, Agnese Fabbri, Alessandra Cassano, Antonino Grassadonia, Claudia Omarini, Federico Piacentini, Andrea Botticelli, Ilaria Bertolini, Angelo Fedele Scinto, Germano Zampa, Maria Mauri, Loretta D'Onofrio, Valentina Sini, Maddalena Barba, Marcello Maugeri-Saccà, Ernesto Rossi, Elisabetta Landucci, Silverio Tomao, Antonio Maria Alberti, Francesco Giotta, Corrado Ficorella, Vincenzo Adamo, Antonio Russo, Vito Lorusso, Katia Cannita, Sandro Barni, Lucio Laudadio, Filippo Greco, Ornella Garrone, Marina Della Giulia, Paolo Marolla, Giuseppe Sanguineti, Barbara Di Cocco, Gennaro Ciliberto, Ruggero De Maria, Teresa Gamucci
We addressed trastuzumab emtansine (T-DM1) efficacy in HER2+ metastatic breast cancer patients treated in real-world practice, and its activity in pertuzumab-pretreated patients. We conducted a retrospective, observational study involving 23 cancer centres, and 250 patients. Survival data were analyzed by Kaplan Meier curves and log rank test. Factors testing significant in univariate analysis were tested in multivariate models. Median follow-up was 15 months and median T-DM1 treatment-length 4 months. Response rate was 41...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881627/structural-basis-of-a-novel-heterodimeric-fc-for-bispecific-antibody-production
#3
Hudie Wei, Haiyan Cai, Yuhao Jin, Pilin Wang, Qingqing Zhang, Yihui Lin, Weixiao Wang, Jinke Cheng, Naiyan Zeng, Ting Xu, Aiwu Zhou
Bispecific antibodies provide an efficient tool for combinational clinical therapy. Here we have engineered a heterodimeric Fc for bispecific antibodies production by combining the knob-into-hole and electrostatic steering strategies where a bulky hydrophobic residue Phe405 of the IgG CH3 interface is mutated to a charged residue Lys and Lys409 of the corresponding CH3 domain is mutated to Ala. The crystal structure of this Fc heterodimer solved here at 2.7Å resolution revealed how these two mutations resulted a complementary binding interface and explained why F405K mutation could effectively inhibit Fc homodimer formation during protein expression...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28856077/exceptional-responses-to-standard-therapy-in-a-patient-with-metastatic-her2-positive-breast-cancer
#4
Carsten Nieder, Bård Mannsåker, Ellinor Haukland
Patients with metastatic breast cancer involving the liver and brain often have short overall survival. Here, we report a case of de novo metastatic breast cancer with multiple liver metastases at initial diagnosis in February 2011 in a 35-year-old Caucasian female patient. The histology was poorly differentiated invasive ductal carcinoma (estrogen and progesterone receptor negative, HER2 positive) and the patient was negative for germline BRCA 1 and 2 mutations. Systemic therapy with trastuzumab and docetaxel was given for six months and then switched to trastuzumab only because of peripheral neuropathy...
June 29, 2017: Curēus
https://www.readbyqxmd.com/read/28840424/economic-evaluation-of-sequencing-strategies-in-her2-positive-metastatic-breast-cancer-in-mexico-a-contrast-between-public-and-private-payer-perspectives
#5
Vakaramoko Diaby, Askal Ayalew Ali, Krystal J Williams, Kyrian Ezendu, Enrique Soto-Perez-de-Celis, Yanin Chavarri-Guerra, Gilberto de Lima Lopes
PURPOSE: Breast cancer is the most common malignancy among women in Mexico. A large proportion of Mexican patients present with advanced disease, and 25% have HER2-positive tumors. We performed a cost-effectiveness analysis of different sequencing strategies of HER2-targeted agents in Mexico according to various payer perspectives. METHODS: A Markov model was constructed to evaluate the cost-effectiveness of four different HER2-targeted treatment sequences among patients with HER2-positive metastatic breast cancer treated in Mexico according to three public and one private payer perspectives...
August 24, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28811974/ex-vivo-assessment-of-drug-response-on-breast-cancer-primary-tissue-with-preserved-microenvironments
#6
Manuele G Muraro, Simone Muenst, Valentina Mele, Luca Quagliata, Giandomenica Iezzi, Alexandar Tzankov, Walter P Weber, Giulio C Spagnoli, Savas D Soysal
Interaction between cancerous, non-transformed cells, and non-cellular components within the tumor microenvironment plays a key role in response to treatment. However, short-term culture or xenotransplantation of cancer specimens in immunodeficient animals results in dramatic modifications of the tumor microenvironment, thus preventing reliable assessment of compounds or biologicals of potential therapeutic relevance. We used a perfusion-based bioreactor developed for tissue engineering purposes to successfully maintain the tumor microenvironment of freshly excised breast cancer tissue obtained from 27 breast cancer patients and used this platform to test the therapeutic effect of antiestrogens as well as checkpoint-inhibitors on the cancer cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28770452/pertuzumab-for-the-neoadjuvant-treatment-of-early-stage-her2-positive-breast-cancer-an-evidence-review-group-perspective-of-a-nice-single-technology-appraisal
#7
REVIEW
Hazel Squires, Abdullah Pandor, Praveen Thokala, John W Stevens, Eva Kaltenthaler, Mark Clowes, Robert Coleman, Lynda Wyld
As part of its single technology appraisal process, the National Institute for Health and Care Excellence invited the manufacturer of pertuzumab (Perjeta(®); Roche Products Limited) to submit evidence of its clinical and cost- effectiveness for the neoadjuvant treatment of women with high-risk, early-stage, HER2-positive breast cancer when used in combination with trastuzumab and chemotherapy. High-risk women included those with locally advanced (including inflammatory) breast cancer and women with high-risk early-stage breast cancer (classified as T2/3 or N1)...
August 2, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/28764748/a-phase-i-trial-of-ganetespib-in-combination-with-paclitaxel-and-trastuzumab-in-patients-with-human-epidermal-growth-factor-receptor-2-her2-positive-metastatic-breast-cancer
#8
Komal Jhaveri, Rui Wang, Eleonora Teplinsky, Sarat Chandarlapaty, David Solit, Karen Cadoo, James Speyer, Gabriella D'Andrea, Sylvia Adams, Sujata Patil, Sofia Haque, Tara O'Neill, Kent Friedman, Francisco J Esteva, Clifford Hudis, Shanu Modi
BACKGROUND: Targeted therapies in HER2-positive metastatic breast cancer significantly improve outcomes but efficacy is limited by therapeutic resistance. HER2 is an acutely sensitive Heat Shock Protein 90 (HSP90) client and HSP90 inhibition can overcome trastuzumab resistance. Preclinical data suggest that HSP90 inhibition is synergistic with taxanes with the potential for significant clinical activity. We therefore tested ganetespib, a HSP90 inhibitor, in combination with paclitaxel and trastuzumab in patients with trastuzumab-refractory HER2-positive metastatic breast cancer...
August 2, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28751451/131i-labeled-anti-her2-camelid-sdab-as-a-theranostic-tool-in-cancer-treatment
#9
Matthias D'Huyvetter, Jens De Vos, Catarina Xavier, Marek Pruszynski, Yann G J Sterckx, Sam Massa, Geert Raes, Vicky Caveliers, Michael Zalutsky, Tony Lahoutte, Nick Devoogdt
<p>Camelid single-domain antibody-fragments (sdAbs) have beneficial pharmacokinetic properties, and those targeted to HER2 can be used for imaging of HER2-overexpressing cancer. Labeled with a therapeutic radionuclide, they may be used for HER2-targeted therapy. Here we describe the generation of a (131)I-labeled sdAb as a theranostic drug to treat HER2-overexpressing cancer.</p> <br />Experimental Design: <p>Anti-HER2 sdAb 2Rs15d was labeled with (131)I using [(131)I]SGMIB and evaluated in vitro Biodistribution was evaluated in two HER2(+) murine xenograft models by micro-SPECT/CT imaging and at necropsy, and under challenge with trastuzumab and pertuzumab...
July 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28751231/concurrent-administration-of-anti-her2-therapy-and-radiotherapy-systematic-review
#10
REVIEW
Fabien Mignot, Zahra Ajgal, Hoping Xu, Arthur Geraud, Jia Yi Chen, Frédérique Mégnin-Chanet, Youlia Kirova
BACKGROUND: Over the past few years, anti-HER2 targeted therapies have proven to be a key treatment in the management of human epidermal growth receptor 2 (HER2)-positive breast cancers, as well as gastrointestinal tract tumors and head and neck tumors. Anti-HER2 therapies administered alone or in combination with chemotherapy have been extensively studied, but only limited robust data are available concerning the safety and efficacy of anti-HER2 molecules in combination with radiotherapy...
July 24, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28737130/effect-of-pertuzumab-trastuzumab-and-docetaxel-in-her2-positive-metastatic-breast-cancer-a-meta-analysis%C3%A2
#11
Tian Tian, Jing Ye, Sihai Zhou
INTRODUCTION: Pertuzumab, as an adjunctive therapy to trastuzumab and docetaxel, has been reported to be potentially beneficial for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. However, the results remain controversial. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of pertuzumab supplementation in patients with HER2-positive metastatic breast cancer. METHODS: Medline, SCOPUS, Google Scholar, Cochrane library databases, EMBASE, Springer, and Science Direct were systematically searched...
September 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28736629/biologic-therapy-in-esophageal-and-gastric-malignancies-current-therapies-and-future-directions
#12
REVIEW
Pamela Samson, A Craig Lockhart
Biologic agents, including targeted antibodies as well as immunomodulators, are demonstrating unparalleled development and study across the entire spectrum of human malignancy. This review summarizes the current state of biologic therapies for esophageal, esophagogastric, and gastric malignancies, including those that target human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), c-Met, mechanistic target of rapamycin (mTOR) and immunomodulators...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28717761/estimation-of-premature-deaths-from-lack-of-access-to-anti-her2-therapy-for-advanced-breast-cancer-in-the-brazilian-public-health-system
#13
Márcio Debiasi, Tomás Reinert, Rafael Kaliks, Gilberto Amorim, Maira Caleffi, Carlos Sampaio, Gustavo Dos Santos Fernandes, Carlos H Barrios
PURPOSE: Patients with human epidermal growth factor receptor 2 (HER2) -positive metastatic tumors treated in the public health system in Brazil do not have access to trastuzumab. This study aimed to estimate the impact of the lack of access to anti-HER2 therapies on the mortality of these patients. METHODS: On the basis of published data, the number of patients with HER2-positive advanced breast cancer in 2016 who should receive anti-HER2 targeted therapy was estimated...
June 2017: Journal of Global Oncology
https://www.readbyqxmd.com/read/28715775/evolution-of-anti-her2-therapies-for-cancer-treatment
#14
REVIEW
Sagun Parakh, Hui K Gan, Adam C Parslow, Ingrid J G Burvenich, Antony W Burgess, Andrew M Scott
The development of HER2-directed monoclonal antibodies and tyrosine kinase inhibitors have provided benefits to cancer patients, as well as produced many insights into the biology of the ErbB receptor family. Current therapies based on ErbB family members have resulted in improved overall survival with associated improvements in quality of life for the cancer patients that respond to treatment. Compared to monotherapy using either two antibodies to block the HER2 receptor blockade or combinatorial approaches with HER2 antibodies and standard therapies has provided additional benefits...
July 6, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28705408/superior-in-vitro-and-in-vivo-activity-of-trastuzumab-emtansine-t-dm1-in-comparison-to-trastuzumab-pertuzumab-and-their-combination-in-epithelial-ovarian-carcinoma-with-high-her2-neu-expression
#15
Gulden Menderes, Elena Bonazzoli, Stefania Bellone, Gary Altwerger, Jonathan D Black, Katherine Dugan, Francesca Pettinella, Alice Masserdotti, Francesco Riccio, Anna Bianchi, Luca Zammataro, Christopher de Haydu, Natalia Buza, Pei Hui, Serena Wong, Gloria S Huang, Babak Litkouhi, Elena Ratner, Dan-Arin Silasi, Masoud Azodi, Peter E Schwartz, Alessandro D Santin
BACKGROUND: Epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy. The objective of this study was to compare the anti-tumor activity of HER2/neu-targeting monoclonal antibodies, trastuzumab (T), pertuzumab (P), combination of trastuzumab and pertuzumab (T+P) and trastuzumab-emtansine (T-DM1) in EOC with high HER2/neu expression. METHODS: Primary EOC cell lines were established and cell blocks were analyzed for HER2/neu expression. Cytostatic, apoptotic and antibody-dependent cell-mediated cytotoxicity (ADCC) activities of T, P, T+P and T-DM1 were evaluated in vitro...
July 10, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28700263/adjuvant-pertuzumab-and-trastuzumab-in-early-her2-positive-breast-cancer
#16
(no author information available yet)
New England Journal of Medicine, Volume 377, Issue 7, Page 702-702, August 2017.
August 17, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28697311/breast-cancer-treatment-induced-cardiotoxicity
#17
REVIEW
Samuel Martel, Christian Maurer, Matteo Lambertini, Noam Pondé, Evandro De Azambuja
Breast cancer is the most frequent cancer affecting women worldwide. In every setting, the majority of women are treated with an evergrowing arsenal of therapeutic agents that have greatly improved their outcomes. However, these therapies can also be associated with significant adverse events. Areas covered: This review aims to thoroughly describe the current state of the evidence regarding the potential cardiotoxicity of agents commonly used in the treatment of breast cancer. These include chemotherapeutic agents, anti-HER2 therapies and CDK4/6 and mTOR inhibitors...
September 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28666920/neoadjuvant-therapy-for-triple-negative-and-her2-positive-early-breast-cancer
#18
Nadia Harbeck, Oleg Gluz
Today, neoadjuvant therapy can be considered a therapy standard in triple negative (TNBC) and in HER2-positive (HER2+) (particularly in HER2+ HR-) early breast cancer (EBC). Patients with a pathological complete response (pCR) will have a very favorable outcome. In TNBC, chemotherapy with anthracyclines and taxanes is standard. Data regarding addition of bevacizumab are rather heterogeneous. Addition of carboplatin improves pCR rates independent of BRCA status; whether this will translate into a survival benefit is still unclear...
August 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28662406/first-report-of-eribulin-in-combination-with-pertuzumab-and-trastuzumab-for-advanced-her2-positive-breast-cancer
#19
Kazuhiro Araki, Ippei Fukada, Hiroyo Yanagi, Kokoro Kobayashi, Tomoko Shibayama, Rie Horii, Shunji Takahashi, Futoshi Akiyama, Shinji Ohno, Yoshinori Ito
BACKGROUND: The efficacy and safety of continuing multiple anti-HER2 therapies in advanced breast cancer (ABC) patients remains unclear. This study investigated eribulin in combination with pertuzumab and trastuzumab for both taxane- and trastuzumab-pretreated HER2-positive ABC patients. METHODS: In a single-institute, single-arm, open-label, phase II trial, HER2-positive ABC patients who had previously received taxanes and trastuzumab were treated with eribulin in combination with pertuzumab and trastuzumab...
June 26, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28625555/adjuvant-pertuzumab-improves-early-breast-cancer-outcomes
#20
Manjulika Das
No abstract text is available yet for this article.
June 15, 2017: Lancet Oncology
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