Daniel Chua

Peter Fasching

Brigette Ma

Sumitra Thongprasert

Lori Wirth

Update on Anti-EGFR Targeted Therapy

Cancers of the esophagus and stomach present a major health burden worldwide. In the past 30 years we have witnessed some interesting shifts in terms of epidemiology of esophago gastric cancers. Regardless of a world region, the majority of patients diagnosed with esophageal or gastric cancers die from progression or recurrence of their disease. While there are many active cytotoxic agents for esophageal and stomach cancers, their impact on the disease course has been modest at best. Median survival for patients with advanced gastroesophageal cancer is still less than a year. Therefore, novel strategies, based on our understanding of biology and genetics, are desperately needed. Epidermal growth factor receptor (EGFR) pathway has been implicated in pathophysiology of many epithelial malignancies, including esophageal and stomach cancers. EGFR inhibitors, small molecule tyrosine kinase inhibitors and monoclonal antibodies, have been explored in patients with esophageal and gastric cancers. It appears that tumors of the distal esophagus and gastroesophageal junction (GEJ) may be more sensitive to EGFR blockade than distal gastric adenocarcinomas. Investigations looking into potential molecular predictors of sensitivity to EGFR inhibitors for patients with esophageal and GEJ cancers are ongoing. While we are still searching for those predictors, it is clear that they will be different from ones identified in lung and colorectal cancers. Further development of EGFR inhibitors for esophageal and GEJ cancers should be driven by better understanding of EGFR pathway disregulation that drives cancer progression in a sensitive patient population.

Tomislav Dragovich

Christopher Campen

Anti-EGFR-Targeted Therapy for Esophageal and Gastric Cancers: An Evolving Concept

Tumor cells that are nonsensitive to anticancer drugs frequently have a multidrug resistant (MDR) phenotype. Many studies with cell lines and patient material have been done to investigate the impact of different resistance markers at protein and mRNA level in drug resistance but with contradictory outcome. In the present study, 26 well-characterised patient-derived non-small cell lung cancer xenografts were used. The known chemosensitivity to etoposide, carboplatin, gemcitabine, paclitaxel and erlotinib was compared to the protein and mRNA expression of BCRP, LRP, MDR1, and MRP1. Further, four of these xenografts were short-term treated to analyse possible regulation mechanisms after therapeutic interventions. We found a borderline correlation between the <i>bcrp</i> mRNA expression and the response of xenografts to etoposide. All other constitutive mRNA and protein expression levels were not correlated to any drug response and were not significantly influenced by a short term treatment. The present results indicate that the expression levels of MDR proteins and mRNA investigated do not play an important role in the chemoresistance of NSCLC in the in vivo situation.

Jana Rolff

Cornelia Dorn

Johannes Merk

Iduna Fichtner

Response of Patient-Derived Non-Small Cell Lung Cancer Xenografts to Classical and Targeted Therapies Is Not Related to Multidrug Resistance Markers

Epidermal growth factor receptor (EGFR) is a cell surface molecule and member of the ErbB family of receptor tyrosine kinases. Its activation leads to proliferation, antiapoptosis, and metastatic spread, making inhibition of this pathway a compelling target. In recent years, an increasing number of clinical trials in the management of solid malignancies have become available indicating the clinical efficacy of anti-EGFR monoclonal antibodies and oral small molecule tyrosine kinase inhibitors (TKIs). This review addresses frequently used EGFR inhibitors, summarizes clinical efficacy data of these new therapeutic agents, and discusses their associated toxicity and management.

Amir Harandi

Aisha S. Zaidi

Abigail M. Stocker

Damian A. Laber

Clinical Efficacy and Toxicity of Anti-EGFR Therapy in Common Cancers

This review will focus on recent advances in the application of antiepidermal growth factor receptor (anti-EGFR) for the treatment of breast cancer. The choice of EGFR, a member of the ErbB tyrosine kinase receptor family, stems from evidence pinpointing its role in various anti-EGFR therapies. Therefore, an increase in our understanding of EGFR mechanism and signaling might reveal novel targets amenable to intervention in the clinic. This knowledge base might also improve existing medical treatment options and identify research gaps in the design of new therapeutic agents. While the approved use of drugs like the dual kinase inhibitor Lapatinib represents significant advances in the clinical management of breast cancer, confirmatory studies must be considered to foster the use of anti-EGFR therapies including safety, pharmacokinetics, and clinical efficacy.

John F. Flynn

Christina Wong

Joseph M. Wu

Anti-EGFR Therapy: Mechanism and Advances in Clinical Efficacy in Breast Cancer

Increased transforming growth factor-<svg     style="vertical-align:-3.56265pt;width:10px;" id="M2" height="16.6625" version="1.1" viewBox="0 0 10 16.6625" width="10"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,12.162)"><use xlink:href="#x1D6FD"/></g>

		
	
</svg> (TGF-<svg     style="vertical-align:-3.56265pt;width:10px;" id="M3" height="16.6625" version="1.1" viewBox="0 0 10 16.6625" width="10"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,12.162)"><use xlink:href="#x1D6FD"/></g>

		
	
</svg>) expression and epidermal growth factor receptor (EGFR) amplification accompany the emergence of highly aggressive human carcinomas. Cooperative signaling between these two growth factor/receptor systems promotes cell migration and synthesis of stromal remodeling factors (i.e., proteases, protease inhibitors) that, in turn, regulate tumor invasion, neo-angiogenesis and inflammation.  ranscript profiling of transformed human cells revealed that genes encoding wound healing, matrix remodeling and cell cycle proteins (i.e., the &#x201C;tissue repair&#x201D; transcriptome) are significantly up-regulated early after growth factor stimulation.  The major inhibitor of plasmin generation, plasminogen activator inhibitor-1 (PAI-1), is among the most highly induced transcripts during the phenotypic transition initiated by TGF-<svg     style="vertical-align:-3.56265pt;width:10px;" id="M4" height="16.6625" version="1.1" viewBox="0 0 10 16.6625" width="10"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,12.162)"><use xlink:href="#x1D6FD"/></g>

		
	
</svg> maximal expression requires EGFR signaling. PAI-1 induction occurs early in the progression of incipient epidermal squamous cell carcinoma (SCC) and is a significant indicator of poor prognosis in epithelial malignancies. Mouse modeling and molecular genetic analysis of complex systems indicates that PAI-1 regulates the temporal/spatial control of pericellular proteolysis, promotes epithelial plasticity, inhibits capillary regression and facilitates stromal invasion. Defining TGF-<svg     style="vertical-align:-3.56265pt;width:10px;" id="M5" height="16.6625" version="1.1" viewBox="0 0 10 16.6625" width="10"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,12.162)"><use xlink:href="#x1D6FD"/></g>

		
	
</svg>1-initiated signaling events that cooperate with an activated EGFR to impact the protease-protease inhibitor balance in the tumor microenvironment is critical to the development of novel therapies for the clinical management of human cancers.

Rohan Samarakoon

Craig E. Higgins

Stephen P. Higgins

Paul J. Higgins

TGF-<svg style="vertical-align:-3.56265pt" height="16.6625" version="1.1" viewBox="0 0 10 16.6625" width="10" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
		<g transform="matrix(.017,-0,0,-.017,.062,12.162)">
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t-62 25.5q-24 0 -43.5 -9t-35 -29.5t-27 -44t-22.5 -63t-19.5 -75.5t-18.5 -91q-57 -294 -68 -380q-26 -190 -35 -200q-26 -31 -97 -37l-4 26q19 9 48 170l77 413q23 121 52.5 187.5t83.5 114.5q70 62 148 62q51 0 88.5 -34t37.5 -91z"/>
		</g>
	</svg> 1-Induced Expression of the Poor Prognosis SERPINE1/PAI-1 Gene Requires EGFR Signaling: A New Target for Anti-EGFR Therapy

The approval of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies in the treatment of metastatic colorectal cancer (CRC) has expanded the armamentarium against this disease. 
                  This paper will review the historical progress and recent clinical developments of anti-EGFR therapies in the treatment of metastatic CRC. Novel strategies of targeting the EGFR pathway to improve efficacy as well as ongoing research in identifying specific molecular predictors of response will be discussed.

Herbert H. Loong

Brigette B. Ma

Anthony T. C. Chan

Update in Antiepidermal Growth Factor Receptor Therapy in the Management of Metastatic Colorectal Cancer

About this journal

<p><em>Journal of Oncology</em> publishes research related to breast cancer, lung cancer, gastrointestinal cancer, skin cancer, head and neck cancer, paediatric oncology, neurooncology as well as genitourinary cancer.</p>


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<p>Chief Editor, Professor Bruno Vincenzi, is an Associate Professor of Medical Oncology at University Campus Bio-Medico, Italy. His research interests include urogenital neoplasms and the pathophysiology and treatment of bone metastases.</p>


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Journal of Oncology publishes research related to breast cancer, lung cancer, gastrointestinal cancer, skin cancer, head and neck cancer, paediatric oncology, neurooncology as well as genitourinary cancer.

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Journal of Oncology | Hindawi

Journal of Oncology

<p>This Issue is now open for submissions.</p>
<p>Papers are published upon acceptance, regardless of the Special Issue publication date.</p>


Journal of Oncology

Update on Anti-EGFR Targeted Therapy

Update on Anti-EGFR Targeted Therapy

Articles

Update on Anti-EGFR Targeted Therapy

Anti-EGFR-Targeted Therapy for Esophageal and Gastric Cancers: An Evolving Concept

Response of Patient-Derived Non-Small Cell Lung Cancer Xenografts to Classical and Targeted Therapies Is Not Related to Multidrug Resistance Markers

Clinical Efficacy and Toxicity of Anti-EGFR Therapy in Common Cancers

Anti-EGFR Therapy: Mechanism and Advances in Clinical Efficacy in Breast Cancer

TGF- 1-Induced Expression of the Poor Prognosis SERPINE1/PAI-1 Gene Requires EGFR Signaling: A New Target for Anti-EGFR Therapy

Update in Antiepidermal Growth Factor Receptor Therapy in the Management of Metastatic Colorectal Cancer