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Her2 colorectal

Hidehito Horinouchi
The mutation or expression of HER family members serves as a therapeutic target for tyrosine kinase inhibitors or monoclonal antibodies in diverse cancers, such as non-small cell lung cancer, breast cancer, gastric cancer, head and neck cancer, colorectal cancer, pancreatic cancer and glioblastoma. HER3, which heterodimerizes with HER1 and HER2, has received much attention as a potential target for anti-EGFR treatment. Patritumab is a novel, fully human monoclonal antibody directed against HER3. Areas covered: In this review article, an overview of the market, chemistry, pharmacodynamics, pharmacokinetics, efficacy, and safety of patritumab is provided based on data from phase I studies, a combination phase I trial, and a randomized phase II trial comparing two doses of patritumab...
October 17, 2016: Expert Opinion on Biological Therapy
Nicola Fusco, Silvano Bosari
Management of cancers of the digestive system has progressed rapidly into the molecular era. Despite the significant recent achievements in the diagnosis and treatment of these patients, the number of deaths for these tumors has currently plateaued. Many investigations have assessed the role of HER2 in tumors of the digestive system in both prognostic and therapeutic settings, with heterogeneous results. Novel testing and treatment guidelines are emerging, in particular in gastric and colorectal cancers. However, further advances are needed...
September 21, 2016: World Journal of Gastroenterology: WJG
Katsuya Nakai, Mien-Chie Hung, Hirohito Yamaguchi
Triple-negative breast cancer (TNBC), which lacks estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), accounts for about 15-20% of breast cancers and is the most aggressive breast cancer subtype. There are currently no effective therapies against metastatic TNBC. Compared with other breast cancer subtypes, EGFR is frequently overexpressed in TNBC and a potential therapeutic target for this disease. There are two types of EGFR inhibitors, small molecular tyrosine kinase inhibitor (TKI) and monoclonal antibody (mAb), for the treatment of cancers, such as non-small cell lung cancer and colorectal cancer...
2016: American Journal of Cancer Research
Chiara Cremolini, Filippo Pietrantonio
In metastatic colorectal cancer, the optimization of upfront treatment and the continuum of care based on patients' exposure to multiple treatment lines have reached a plateau of efficacy. Therefore, a paradigm shift is ongoing towards precision medicine and personalized treatments based on the specific molecular features of the disease. In this perspective, the improved knowledge of disease biology coming from the lab has prompted a rapid translation from bench to bedside of newer targeted strategies. Here, we focus on the most promising biomarkers already included or close to adoption in daily clinical practice...
September 20, 2016: Tumori
Benjamin Lu, Brooke A Green, Jacqueline M Farr, Flávia C M Lopes, Terence J Van Raay
The Wnt signaling pathway is intricately involved in many aspects of development and is the root cause of an increasing number of diseases. For example, colorectal cancer is the second leading cause of death in the industrialized world and aberration of Wnt signaling within the colonic stem cell is the cause of more than 90% of these cancers. Despite our advances in successfully targeting other pathways, such as Human Epidermal Growth Factor Receptor 2 (HER2), there are no clinically relevant therapies available for Wnt-related diseases...
September 1, 2016: Cancers
Cristiana Lo Nigro, Vincenzo Ricci, Daniela Vivenza, Cristina Granetto, Teresa Fabozzi, Emanuela Miraglio, Marco C Merlano
AIM: To reviewing genetic and epigenetic make-up of metastatic colorectal cancers (mCRCs) addicted to epidermal growth factor receptor (EGFR) signalling. METHODS: The present study summarizes the potential value of prognostic and predictive biomarkers in selecting mCRC patients treated with anti-EGFR therapy. A meta-analysis was performed using a systematic search of PubMed, Medline and Web of Science to identify eligible papers until March 21(st), 2016 using these following terms: ''colorectal cancer'', "predictive biomarkers'', "anti-EGFR therapy", "KRAS", "NRAS'', "PIK3CA", "TP53", "PTEN", ''EGFR", "MET", "HER2", "epiregulin", "amphiregulin", "prognostic biomarkers", "BRAF", "miRNA" and "antibody-dependent cell-mediated cytotoxicity (ADCC) activity"...
August 14, 2016: World Journal of Gastroenterology: WJG
Giulia Bon, Rossella Loria, Carla Azzurra Amoreo, Alessandra Verdina, Isabella Sperduti, Arianna Mastrofrancesco, Silvia Soddu, Maria Grazia Diodoro, Marcella Mottolese, Matilde Todaro, Giorgio Stassi, Michele Milella, Ruggero De Maria, Rita Falcioni
Although the medical treatment of colorectal cancer has evolved greatly in the last years, a significant portion of early-stage patients develops recurrence after therapies. The current clinical trials are directed to evaluate new drug combinations and treatment schedules. By the use of patient-derived or established colon cancer cell lines, we found that the tyrosine kinase receptor HER3 is involved in the mechanisms of resistance to therapies. In agreement, the immunohistochemical analysis of total and phospho-HER3 expression in 185 colorectal cancer specimens revealed a significant correlation with lower disease-free survival...
August 19, 2016: Oncotarget
Claudia Burz, Ben Youssef Mohamed Aziz, Loredana Bălăcescu, Luminiţa Leluţiu, Rareş Buiga, Gabriel Samasca, Alexandru Irimie, Cosmin Lisencu
BACKGROUND AND AIMS: The aim of this study was to investigate the value of serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) correlated with some tissue molecules as predictive markers for recurrence in colon cancer. METHODS: A total of 30 patients diagnosed with colon cancer stage II or III who underwent optimal surgery were enrolled in study. Tumor markers CEA and CA 19-9 were determined before surgery. Tumor samples were prepared using tissue microarray kit (TMA) then stained for different cellular markers (Ki 67, HER2, BCL2, CD56, CD4, CD8) and analyzed using Inforatio programme for quantitative determination...
2016: Clujul Medical (1957)
Valentina Fanotto, Elena Ongaro, Karim Rihawi, Antonio Avallone, Nicola Silvestris, Lorenzo Fornaro, Enrico Vasile, Lorenzo Antonuzzo, Francesco Leone, Gerardo Rosati, Francesco Giuliani, Roberto Bordonaro, Mario Scartozzi, Giovanna De Maglio, Francesca V Negri, Gianpiero Fasola, Giuseppe Aprile
HER-2 (ErbB-2, c-erbB2 or Her2/neu), a member of the HER-family, is directly involved in the pathogenesis and progression of several human cancers; as such, it is also often considered as a poor prognostic factor. Following the revolutionary impact of anti-HER-2 therapy in breast cancer patients, the role of HER-2 and its blockade has also been extensively evaluated in other tumor types, including gastric and colorectal adenocarcinoma. The aims of this review are to recall the important results achieved with the use of HER-2 inhibitors in both gastric and colorectal cancer, and to discuss on the updates available on the role of HER-2 as prognostic and predictive factor in these malignancies...
August 12, 2016: Oncotarget
Julian Holch, Sebastian Stintzing, Volker Heinemann
Palliative chemotherapy for metastatic colorectal cancer has undergone substantial changes in recent years. The implementation of modern biologicals in the treatment has substantially improved overall survival up to 30 months. With the increasing number of therapeutic options, the question of optimal treatment sequence arises, which is addressed in current studies like FIRE 4 or STRATEGIC-1. Furthermore, clinical and molecular biomarkers to predict efficacy and tolerability are urgently needed. Today, the detection of activating RAS mutations is the only validated biomarker which precludes patients from anti-EGFR treatment...
June 2016: Visc Med
Ace J Hatch, Alexander B Sibley, Mark D Starr, J Chris Brady, Chen Jiang, Jingquan Jia, Daniel L Bowers, Herbert Pang, Kouros Owzar, Donna Niedzwiecki, Federico Innocenti, Alan P Venook, Herbert I Hurwitz, Andrew B Nixon
Circulating protein markers were assessed in patients with colorectal cancer (CRC) treated with cetuximab in CALGB 80203 to identify prognostic and predictive biomarkers. Patients with locally advanced or metastatic CRC received FOLFOX or FOLFIRI chemotherapy (chemo) or chemo in combination with cetuximab. Baseline plasma samples from 152 patients were analyzed for six candidate markers [epidermal growth factor (EGF), heparin-binding EGF (HBEGF), epidermal growth factor receptor (EGFR), HER2, HER3, and CD73]...
September 2016: Cancer Medicine
N Cherny, R Sullivan, J Torode, M Saar, A Eniu
BACKGROUND: The management of cancer is predicated on the availability and affordability of anticancer therapies, which may be either curative or noncurative. AIM: The primary aims of the study were to evaluate (i) the formulary availability of licensed antineoplastic medicines across Europe; (ii) patient out-of-pocket costs for the medications and (iii) the actual availability of the medication for a patient with a valid prescription. MATERIALS AND METHODS: The survey tool was based on the previous ESMO studies that addressed the availability and accessibility of opioids for the management of cancer pain...
August 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Mari Iida, Harsh Bahrar, Toni M Brand, Hannah E Pearson, John P Coan, Rachel A Orbuch, Bailey G Flanigan, Adam D Swick, Prashanth J Prabakaran, Johan Lantto, Ivan D Horak, Michael Kragh, Ravi Salgia, Randy J Kimple, Deric L Wheeler
Cetuximab, an antibody against the EGFR, has shown efficacy in treating head and neck squamous cell carcinoma (HNSCC), metastatic colorectal cancer, and non-small cell lung cancer (NSCLC). Despite the clinical success of cetuximab, many patients do not respond to cetuximab. Furthermore, virtually all patients who do initially respond become refractory, highlighting both intrinsic and acquired resistance to cetuximab as significant clinical problems. To understand mechanistically how cancerous cells acquire resistance, we previously developed models of acquired resistance using the H226 NSCLC and UM-SCC1 HNSCC cell lines...
September 2016: Molecular Cancer Therapeutics
Shruti Rakesh Tiwari, Prasun Mishra, Jame Abraham
HER2 gene amplification and receptor overexpression is identified in 20% to 25% of human breast cancers. Use of targeted therapy for HER2-amplified breast cancer has led to improvements in disease-free and overall survival in this subset of patients. Neratinib is an oral pan HER inhibitor, that irreversibly inhibits the tyrosine kinase activity of epidermal growth factor receptor (EGFR or HER1), HER2, and HER4, which leads to reduced phosphorylation and activation of downstream signaling pathways. Neratinib is currently being tested in a number of clinical trials for its safety and efficacy in lung cancer, and colorectal, bladder, and breast cancers...
May 29, 2016: Clinical Breast Cancer
Sherri Z Millis, Sadakatsu Ikeda, Sandeep Reddy, Zoran Gatalica, Razelle Kurzrock
Importance: Molecular aberrations in the phosphatidylinositol-3-kinase (PI3K) pathway drive tumorigenesis. Frequently co-occurring alterations in hormone receptors and/or human epidermal growth factor receptor 2 (HER2) may be relevant to mechanisms of response and resistance. Objective: To identify patterns of aberration in the PI3K and interactive pathways that might lead to targeted therapy opportunities in clinical practice. Design, Setting, and Participants: From January 2013 through December 2014, 19 784 consecutive tumor samples (>40 cancer types) were sent from thousands of clinicians in 60 countries to a single commercial laboratory for molecular profiling, including next generation sequencing, protein expression (immunohistochemical analysis [IHC]), and gene amplification (fluorescent in situ hybridization or chromogenic in situ hybridization)...
July 7, 2016: JAMA Oncology
I De Pauw, A Wouters, J Van den Bossche, M Peeters, P Pauwels, V Deschoolmeester, J B Vermorken, F Lardon
Targeting the epidermal growth factor receptor (EGFR) with monoclonal antibodies (mAbs) or tyrosine kinase inhibitors (TKI) has been an interesting therapeutic strategy because aberrant activation of this receptor plays an important role in the tumorgenesis of many cancer types, including colorectal cancer (CRC). After the initial promising results of EGFR-targeted therapies, therapeutic resistance is a major clinical problem. In order to overcome resistance to these EGFR-targeted therapies, new treatment options are necessary...
October 2016: Pharmacology & Therapeutics
Michael Pohl, Wolff Schmiegel
BACKGROUND: Colorectal cancer (CRC) is the third most common cancer type in Western countries. Significant progress has been made in the last decade in the therapy of metastatic CRC (mCRC) with a median overall survival (OS) of patients exceeding 30 months. The integration of biologic targeted therapies and anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MABs) in the treatment of patients with genomically selected all-RAS wild-type mCRC leads to a significant progress in advanced incurable disease state...
2016: Digestive Diseases
R Němeček, M Svoboda, O Slabý
BACKGROUND: The combination of modern systemic chemotherapy and anti-EGFR monoclonal antibodies improves overall survival and quality of life for patients with metastatic colorecal cancer. By contrast, the addition of anti-EGFR therapy to the treatment regime of resistant patients may lead to worse progression-free survival and overall survival. Therefore, identifying sensitive and resistant patients prior to targeted therapy of metastatic colorecal cancer is a key point during the initial decision making process...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
(no author information available yet)
Preliminary findings from MyPathway, an ongoing phase II basket trial, indicate that matching molecular abnormalities of patients' tumors to relevant targeted therapies-albeit outside a given drug's FDA-approved indication-is both feasible and promising. Notably, patients with HER2-amplified colorectal, bladder, and biliary cancers responded well to the combination of trastuzumab and pertuzumab.
July 2016: Cancer Discovery
Camilla Natasha Cederbye, Jesper Andreas Palshof, Tine Plato Hansen, Anne Katrine Duun-Henriksen, Dorte Linnemann, Jan Stenvang, Dorte Lisbet Nielsen, Nils Brünner, Birgitte Martine Viuff
Overexpression of the ATP-dependent drug efflux pump ABCG2 is a major molecular mechanism of multidrug resistance in cancer and might be a predictive biomarker for drug response. Contradictory results have been reported for immunohistochemical studies of ABCG2 protein expression in colorectal cancer (CRC), probably because of the use of different antibodies and scoring approaches. In this study, we systematically studied six commercially available anti-ABCG2 antibodies, using cell lines with up-regulation of ABCG2, and selected one antibody for validation in CRC tissue...
2016: Scientific Reports
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