Epidermal Growth Factor Receptor Inhibitors: Current Status and Future Directions

Chen, Alice; Cleck, Jessica N.; Coelho, Rochelle P.; Dancey, Janet

doi:10.1016/j.currproblcancer.2009.10.002

Cited by 8 publications

(7 citation statements)

References 149 publications

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“…EGFR is highly expressed in a variety of epithelial tumors, such as non-small cell lung cancer, head and neck squamous cell carcinoma (HNSCC), colorectal cancer (CRC), and breast cancer [4], [5]. Multiple anti-EGFR agents have been developed and have exhibited significant anti-tumor activities in these cancers [6], [7].…”

Section: Introductionmentioning

confidence: 99%

Epidermal Growth Factor Receptor (EGFR)-RAS Signaling Pathway in Penile Squamous Cell Carcinoma

Gou

Qiu

et al. 2013

PLoS ONE

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Penile Squamous Cell Carcinoma (SCC) is a rare cancer with poor prognosis and limited response to conventional chemotherapy. The genetic and epigenetic alterations of Epidermal Growth Factor Receptor (EGFR)-RAS-RAF signaling in penile SCC are unclear. This study aims to investigate four key members of this pathway in penile SCC. We examined the expression of EGFR and RAS-association domain family 1 A (RASSF1A) as well as the mutation status of K-RAS and BRAF in 150 cases of penile SCC. EGFR and RASSF1A expression was evaluated by immunohistochemistry. KRAS mutations at codons 12 and 13, and the BRAF mutation at codon 600 were analyzed on DNA isolated from formalin fixed paraffin embedded tissues by direct genomic sequencing. EGFR expression was positive in all specimens, and its over-expression rate was 92%. RASSF1A expression rate was only 3.42%. Significant correlation was not found between the expression of EGFR or RASSF1A and tumor grade, pT stage or lymph node metastases. The detection of KRAS and BRAF mutations analysis was performed in 94 and 83 tumor tissues, respectively. We found KRAS mutation in only one sample and found no BRAF V600E point mutation. In summary, we found over-expression of EGFR in the majority cases of penile SCC, but only rare expression of RASSF1A, rare KRAS mutation, and no BRAF mutation in penile SCC. These data suggest that anti-EGFR agents may be potentially considered as therapeutic options in penile SCC.

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Section: Introductionmentioning

confidence: 99%

Epidermal Growth Factor Receptor (EGFR)-RAS Signaling Pathway in Penile Squamous Cell Carcinoma

Gou

Qiu

et al. 2013

PLoS ONE

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“…Inhibitors of the EGFR have been used for therapy of several types of human cancer (Chen et al, 2009). The two major classes of inhibitors are monoclonal antibodies that interfere with ligand binding and small molecule kinase inhibitors that selectively block receptor activation.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of the epidermal growth factor receptor by erlotinib prevents immortalization of human cervical cells by Human Papillomavirus type 16

Woodworth¹,

Diefendorf²,

Jette³

et al. 2011

Virology

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The Human Papillomavirus type-16 (HPV-16) E6 and E7 oncogenes are selectively retained and expressed in cervical carcinomas, and expression of E6 and E7 is sufficient to immortalize human cervical epithelial cells. Expression of the epidermal growth factor receptor (EGFR) is often increased in cervical dysplasia and carcinoma, and HPV oncoproteins stimulate cell growth via the EGF-R pathway. We found that erlotinib, a specific inhibitor of EGFR tyrosine kinase activity, prevented immortalization of cultured human cervical epithelial cells by the complete HPV-16 genome or the E6/E7 oncogenes. Erlotinib stimulated apoptosis in cells that expressed HPV-16 E6/E7 proteins and induced senescence in a subpopulation of cells that did not undergo apoptosis. Since immortalization by HPV E6/E7 is an important early event in cervical carcinogenesis, the EGFR is a potential target for chemoprevention or therapy in women who have a high risk for cervical cancer.

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“…It has been hypothesized that EGFR overexpression increases signal generation and activates downstream pathways making cells grow more aggressively and develop invasive characteristics [9]. There are two major categories of anti-EGFR therapeutics: antibodies binding to the extracellular ligand-binding region and small-molecule tyrosine-kinase inhibitors (TKIs) that compete with ATP for binding to the kinase domain [10]. The Food and Drug Administration (FDA) has approved the monoclonal antibodies cetuximab and panitumumab in the treatment of colorectal and head and neck cancer and erlotinib for lung and pancreatic cancer [10].…”

Section: Introductionmentioning

confidence: 99%

“…There are two major categories of anti-EGFR therapeutics: antibodies binding to the extracellular ligand-binding region and small-molecule tyrosine-kinase inhibitors (TKIs) that compete with ATP for binding to the kinase domain [10]. The Food and Drug Administration (FDA) has approved the monoclonal antibodies cetuximab and panitumumab in the treatment of colorectal and head and neck cancer and erlotinib for lung and pancreatic cancer [10]. Finding EGFR overexpressed in ACC has triggered interest to investigate whether patients benefit from such targeted therapies.…”

Section: Introductionmentioning

confidence: 99%

The Role of EGFR Inhibitors in the Treatment of Metastatic Anal Canal Carcinoma: A Case Series

Saif

Kontny

Syrigos

et al. 2011

Journal of Oncology

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Anal cancer patients who have exhibited disease progression after having received all approved drugs pose a major therapeutic challenge. In addition to cytotoxic agents, novel targeted agents are being developed and have an established role in the treatment of many solid tumors, including colon cancer. However, their role in anal cancer is yet to be determined. Most anal malignancies are squamous cell carcinomas often strongly expressing epidermal growth factor receptors (EGFRs). Targeting the latter seems to result in favorable changes in tumor growth. We present three cases of refractory anal cancers, treated with EGFR inhibitors, after having received the recommended chemotherapy regimens. We conclude that EGFR inhibitors may play a vital role in the treatment of anal cancer and we suggest that large trials are be conducted in order to clarify their efficacy and to improve therapeutic management.

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Epidermal Growth Factor Receptor Inhibitors: Current Status and Future Directions

Cited by 8 publications

References 149 publications

Epidermal Growth Factor Receptor (EGFR)-RAS Signaling Pathway in Penile Squamous Cell Carcinoma

Epidermal Growth Factor Receptor (EGFR)-RAS Signaling Pathway in Penile Squamous Cell Carcinoma

Inhibition of the epidermal growth factor receptor by erlotinib prevents immortalization of human cervical cells by Human Papillomavirus type 16

The Role of EGFR Inhibitors in the Treatment of Metastatic Anal Canal Carcinoma: A Case Series

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