Antiepidermal Growth Factor Receptor Monoclonal Antibodies: Applications in Colorectal Cancer

Azizi, Efat; Kittai, Adam; Kozuch, Peter

doi:10.1155/2012/198197

Cited by 3 publications

(4 citation statements)

References 51 publications

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“…EGFR expression correlates with reduced survival of patients with glioma 18 , breast 19 , colorectal 20 , non-small cell lung 21 , prostate 22 , bladder, cervical, esophageal, ovarian, and head and neck cancers 23 . Recently, novel anticancer drugs have been developed that target EGFR family members and other growth factor receptors 24 - 26 . Cetuximab is an example of a monoclonal antibody that has high affinity for, and blocks, the ligand-binding domain of EGFR, thereby preventing downstream signaling 24 .…”

Section: Introductionmentioning

confidence: 99%

“…Recently, novel anticancer drugs have been developed that target EGFR family members and other growth factor receptors 24 - 26 . Cetuximab is an example of a monoclonal antibody that has high affinity for, and blocks, the ligand-binding domain of EGFR, thereby preventing downstream signaling 24 . It is a well-established therapeutic agent in oncology, and is increasingly used in clinics, mainly in combination with chemo- or radiotherapy 27 .…”

Section: Introductionmentioning

confidence: 99%

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A High-Affinity Repebody for Molecular Imaging of EGFR-Expressing Malignant Tumors

Yun¹,

Kim²,

Lee³

et al. 2017

Theranostics

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The accurate detection of disease-related biomarkers is crucial for the early diagnosis and management of disease in personalized medicine. Here, we present a molecular imaging of human epidermal growth factor receptor (EGFR)-expressing malignant tumors using an EGFR-specific repebody composed of leucine-rich repeat (LRR) modules. The repebody was labeled with either a fluorescent dye or radioisotope, and used for imaging of EGFR-expressing malignant tumors using an optical method and positron emission tomography. Our approach enabled visualization of the status of EGFR expression, allowing quantitative evaluation in whole tumors, which correlated well with the EGFR expression levels in mouse or patients-derived colon cancers. The present approach can be effectively used for the accurate detection of EGFR-expressing cancers, assisting in the development of a tool for detecting other disease biomarkers.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A High-Affinity Repebody for Molecular Imaging of EGFR-Expressing Malignant Tumors

Yun¹,

Kim²,

Lee³

et al. 2017

Theranostics

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“… 6 Targeted inhibition of EGFR using monoclonal antibodies like cetuximab and panitumumab, represents one of the standard therapies of metastatic CRC and—combined with chemotherapies—provides survival benefit over chemotherapy alone. 7 However, treatment response is limited to patients without activating KRAS mutations. 4 Interestingly, treatment response does not correlate with the levels of EGFR expression in tumor cells.…”

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confidence: 99%

EGFR in Tumor-Associated Myeloid Cells Promotes Development of Colorectal Cancer in Mice and Associates With Outcomes of Patients

et al. 2017

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Background & AimsInhibitors of the epidermal growth factor receptor (EGFR) are the first-line therapy for patients with metastatic colorectal tumors without RAS mutations. However, EGFR inhibitors are ineffective in these patients, and tumor level of EGFR does not associate with response to therapy. We screened human colorectal tumors for EGFR-positive myeloid cells and investigated their association with patient outcome. We also performed studies in mice to evaluate how EGFR expression in tumor cells and myeloid cells contributes to development of colitis-associated cancer and ApcMin-dependent intestinal tumorigenesis.MethodsWe performed immunohistochemical and immunofluorescent analyses of 116 colorectal tumor biopsies to determine levels of EGFR in tumor and stroma; we also collected information on tumor stage and patient features and outcomes. We used the Mann-Whitney U and Kruskal-Wallis tests to correlate tumor levels of EGFR with tumor stage, and the Kaplan-Meier method to estimate patients’ median survival time. We performed experiments in mice lacking EGFR in intestinal epithelial cells (Villin-Cre; Egfrf/f and Villin-CreERT2; Egfrf/f mice) or myeloid cells (LysM-Cre; Egfrf/f mice) on a mixed background. These mice were bred with ApcMin/+ mice; colitis-associated cancer and colitis were induced by administration of dextran sodium sulfate (DSS), with or without azoxymethane (AOM), respectively. Villin-CreERT2 was activated in developed tumors by administration of tamoxifen to mice. Littermates that expressed full-length EGFR were used as controls. Intestinal tissues were collected; severity of colitis, numbers and size of tumors, and intestinal barrier integrity were assessed by histologic, immunohistochemical, quantitative reverse transcription polymerase chain reaction, and flow cytometry analyses.ResultsWe detected EGFR in myeloid cells in the stroma of human colorectal tumors; myeloid cell expression of EGFR associated with tumor metastasis and shorter patient survival time. Mice with deletion of EGFR from myeloid cells formed significantly fewer and smaller tumors than the respective EGFR-expressing controls in an ApcMin/+ background as well as after administration of AOM and DSS. Deletion of EGFR from intestinal epithelial cells did not affect tumor growth. Furthermore, tamoxifen-induced deletion of EGFR from epithelial cells of established intestinal tumors in mice given AOM and DSS did not reduce tumor size. EGFR signaling in myeloid cells promoted activation of STAT3 and expression of survivin in intestinal tumor cells. Mice with deletion of EGFR from myeloid cells developed more severe colitis after DSS administration, characterized by increased intestinal inflammation and intestinal barrier disruption, than control mice or mice with deletion of EGFR from intestinal epithelial cells. EGFR-deficient myeloid cells in the colon of DSS-treated LysM-Cre; Egfrf/f mice had reduced expression of interleukin 6 (IL6), and epithelial STAT3 activation was reduced compared with controls. Administration of re...

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“…Although increasing evidence points to a direct binding between RASSF1A and K-ras, its association to and its effect on K-ras are still not decided [22]. Furthermore, EGFR is expressed in 80% of CRC, and several recent and concordant clinical studies have shown that EGFR status is independent of K-ras mutations in colorectal tumors [23]. However, whether RASSF1A expression is related to K-ras mutation, EGFR status, and clinical feature of CRCs still needs to be clarified.…”

Section: Introductionmentioning

confidence: 99%

Loss of RASSF1A Expression in Colorectal Cancer and Its Association with K-ras Status

Cao

Chen

Tang

et al. 2013

BioMed Research International

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Background. The RAS-association domain family 1 A (RASSF1A) is a classical member of RAS effectors regulating cell proliferation and apoptosis. Loss of RASSF1A expression may shift the balance towards a growth-promoting effect without the necessity of activating K-ras mutations. Its potential association with K-ras mutations in colorectal cancer (CRC) is unclear. Methods. RASSF1A expression was examined in normal mucosa, adenoma, and tumor tissues of colon and rectum, respectively. We examined the association of RASSF1A expression, mutations of K-ras, and EGFR status in 76 primary CRCs. The relationship between clinicopathological characteristics and RASSF1A expression was also analyzed. Results. RASSF1A expression level decreased progressively in normal mucosa, adenoma and, tumor tissues, and the loss of RASSF1A expression occurred more frequently in tumor tissues. Of 76 primary CRCs, loss of RASSF1A expression and/or K-ras mutations were detected in 77% cases. Loss of RASSF1A expression was more frequent in K-ras wild-type than in mutation cases (63% versus 32%, P = 0.011). Conclusions. Our study indicates that loss of RASSF1A may be involved in pathogenesis of CRC, its expression was found predominantly in K-ras wild-type CRCs, suggesting that it may be another way of affecting RAS signaling, in addition to K-ras mutations.

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Antiepidermal Growth Factor Receptor Monoclonal Antibodies: Applications in Colorectal Cancer

Cited by 3 publications

References 51 publications

A High-Affinity Repebody for Molecular Imaging of EGFR-Expressing Malignant Tumors

A High-Affinity Repebody for Molecular Imaging of EGFR-Expressing Malignant Tumors

EGFR in Tumor-Associated Myeloid Cells Promotes Development of Colorectal Cancer in Mice and Associates With Outcomes of Patients

Loss of RASSF1A Expression in Colorectal Cancer and Its Association with K-ras Status

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