INT117348

Context Info Confidence 0.61 First Reported 2000 Last Reported 2010 Negated 3 Speculated 4 Reported most in Body Documents 75 Total Number 82 Disease Relevance 47.73 Pain Relevance 3.09

endosome (EGFR) cell morphogenesis (EGFR) Golgi apparatus (EGFR) endoplasmic reticulum (EGFR) intracellular (EGFR) enzyme binding (EGFR)

Anatomy Link Frequency lung 3 brain 1 bladder 1 NCI-H292 1 neck 1 EGFR (Homo sapiens)

Pain Link Frequency Relevance Heat Potency 10 100.00 antagonist 30 99.96 addiction 37 99.84 cINOD 101 98.08 lidocaine 12 97.96 Central nervous system 94 96.96 Cannabinoid 84 96.72 Inflammation 169 96.00 Endocannabinoid 50 95.96 Pain 135 93.36

Disease Link Frequency Relevance Heat Cancer 2872 100.00 Proteinuria 44 100.00 Breast Cancer 541 99.84 Ovarian Cancer 92 99.84 Prostate Cancer 190 99.74 Carcinoma 96 99.52 Adenocarcinoma 120 99.48 Lung Cancer 322 99.44 Malignant Neoplastic Disease 165 99.44 Apoptosis 350 99.36

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Speculation

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Disease term

A series of landmark studies have established the role of cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), in the treatment of locoregionally advanced and potentially curable HNSCC as well as in patients with incurable recurrent and/or metastatic HNSCC.7 This review summarizes current data available regarding the evolving use of cetuximab in the treatment of incurable HNSCC.

Regulation (targeting) of EGFR

1) Confidence 0.61 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2921255 Disease Relevance 0.85 Pain Relevance 0

A series of landmark studies have established the role of cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), in the treatment of locoregionally advanced and potentially curable HNSCC as well as in patients with incurable recurrent and/or metastatic HNSCC.7 This review summarizes current data available regarding the evolving use of cetuximab in the treatment of incurable HNSCC.

Regulation (targeting) of epidermal growth factor receptor

2) Confidence 0.61 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2921255 Disease Relevance 0.85 Pain Relevance 0

With the completion of the growth processes of the brain in adulthood the EGFR is down regulated.

Regulation (regulated) of EGFR in brain

3) Confidence 0.59 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2894859 Disease Relevance 0.61 Pain Relevance 0.11

To investigate the effects on EGFR regulation, AGS cells were transfected with a full-length and truncated EGFR luciferase (luc) reporter.

Spec (investigate) Regulation (regulation) of EGFR in AGS

4) Confidence 0.55 Published 2007 Journal Am. J. Gastroenterol. Section Body Doc Link 17617207 Disease Relevance 0.09 Pain Relevance 0

Impact of EGFR mutations on survival and time to progression (TTP)

Regulation (Impact) of EGFR

5) Confidence 0.45 Published 2010 Journal World J Surg Oncol Section Body Doc Link PMC2970593 Disease Relevance 0.21 Pain Relevance 0

Recapitulation of EGFR mutations in lung cancer cells in vitro have demonstrated that it is an example of an 'oncogenic addiction' mutation which provides a biologic explanation for the improved outcome seen in this EGFR mutant NSCLC group relative to the wild type group[9].

Regulation (Recapitulation) of EGFR in lung associated with addiction, lung cancer and non-small-cell lung cancer

6) Confidence 0.45 Published 2010 Journal World J Surg Oncol Section Body Doc Link PMC2970593 Disease Relevance 1.56 Pain Relevance 0.05

EGFR-dependent transcriptional programs are also affected by cetuximab, which reduces angiogenesis, tumor invasiveness, and metastatic spread (Harding and Burtness 2005).

Regulation (affected) of EGFR associated with cancer

7) Confidence 0.45 Published 2007 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2721306 Disease Relevance 0.33 Pain Relevance 0.04

Clearly, the selection of patients based on EGFR expression is no longer sufficient, inasmuch as response rates appear independent of EGFR staining intensity (Cunningham et al 2004; Lenz et al 2006).

Neg (independent) Spec (appear) Regulation (independent) of EGFR

8) Confidence 0.45 Published 2007 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2721306 Disease Relevance 0.64 Pain Relevance 0

First, it is important to thoroughly investigate thesignaling pathway and mechanism of EGFR

Spec (investigate) Regulation (mechanism) of EGFR

9) Confidence 0.45 Published 2009 Journal Journal of Oncology Section Body Doc Link PMC2668926 Disease Relevance 0.62 Pain Relevance 0

anti-EGFR therapy has moderate clinical efficacy not only on EGFR-expressing

Regulation (efficacy) of EGFR-expressing

10) Confidence 0.45 Published 2009 Journal Journal of Oncology Section Body Doc Link PMC2668926 Disease Relevance 0.52 Pain Relevance 0

anomalous EGFR expression; in this case, scrutiny of the structure of EGFR and

Regulation (scrutiny) of EGFR

11) Confidence 0.45 Published 2009 Journal Journal of Oncology Section Body Doc Link PMC2668926 Disease Relevance 0.58 Pain Relevance 0

Multivariable logistic regression analysis was performed on the effect of the EGFR polymorphism and other risk factors for ACS.

Regulation (effect) of EGFR associated with acute coronary syndrome

12) Confidence 0.45 Published 2008 Journal BMC Med Genet Section Body Doc Link PMC2515827 Disease Relevance 0.25 Pain Relevance 0

The effect of the EGFR antagonist occurs without any change in the pattern and the severity of toxicity usually associated with head and neck radiation.

Regulation (effect) of EGFR in neck associated with toxicity and antagonist

13) Confidence 0.45 Published 2010 Journal Cancer management and research Section Body Doc Link PMC3004587 Disease Relevance 0.77 Pain Relevance 0.05

Preclinical models have suggested that vascular endothelial growth factor (VEGF) production by tumor cells may counteract the antitumor effects of EGFR inhibition.

Regulation (effects) of EGFR associated with cancer

14) Confidence 0.45 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2921255 Disease Relevance 0.60 Pain Relevance 0

By selecting drugs for responsive patients, we would also minimize the financial burden on the current healthcare system.64 In targeting the EGFR pathway, panitumumab has been shown to be well tolerated and effective in the treatment of metastatic colorectal cancer.

Regulation (targeting) of EGFR associated with colorectal cancer

15) Confidence 0.44 Published 2009 Journal OncoTargets and therapy Section Body Doc Link PMC2886332 Disease Relevance 0.52 Pain Relevance 0

These factors were not addressed in the other studies and could potentially account for the differences in EGFR and EGFRvIII prognostic impact between these studies, especially if there was a significant incidence of these in a small series.

Regulation (differences) of EGFR

16) Confidence 0.44 Published 2005 Journal J Transl Med Section Body Doc Link PMC1298339 Disease Relevance 0.95 Pain Relevance 0.07

Since EGFR expression is often found in NSCLC cells [17, 18], it has been the focus of efforts to develop new agents that target the EGFR pathway.

Regulation (target) of EGFR associated with non-small-cell lung cancer

17) Confidence 0.42 Published 2010 Journal Current Gerontology and Geriatrics Research Section Body Doc Link PMC2905690 Disease Relevance 0.43 Pain Relevance 0

To determine the effect of gefitinib on the phosphorylation status of EGFR, Ist-Mes-1, Ist-Mes-2 and MPP89, cells were seeded in T25 flask in full culture media for 24 h. 45 mins after the addition of gefitinib, EGF (final concentration 100 ng/ml) was added.

Spec (determine) Regulation (effect) of EGFR

18) Confidence 0.38 Published 2010 Journal Mol Cancer Section Body Doc Link PMC2828989 Disease Relevance 0.10 Pain Relevance 0

The positive control for COX-2, VEGF, and EGFR was gastric adenocarcinoma, and the negative control was the normal mucosa around tumors on the same slide.

Regulation (control) of EGFR associated with adenocarcinoma and cancer

19) Confidence 0.38 Published 2010 Journal Journal of the Korean Society of Coloproctology Section Body Doc Link PMC2998021 Disease Relevance 0.60 Pain Relevance 0.03

ZD 1839 (gefitinib) is an example of an orally active, selective EGFR tyrosine kinase inhibitor, which has shown extensive preclinical activity.

Regulation (selective) of EGFR

20) Confidence 0.38 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2575526 Disease Relevance 0.77 Pain Relevance 0

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