Understanding EGFR Signaling in Breast Cancer and Breast Cancer Stem Cells: Overexpression and Therapeutic Implications

Alanazi, Ibrahim O.; Khan, Zahid

doi:10.7314/apjcp.2016.17.2.445

Cited by 38 publications

(37 citation statements)

References 67 publications

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“…The evidence for the impact of EGFR on survival and recurrence deserves to be explored in the Pakistani population as it suffers from a record high prevalence of OSCC and patients encounter inadequate diagnostic and treatment measures. EGFR has the potential to become a target for therapeutic measures in the form of monoclonal antibodies or tyrosine kinase inhibitors as has been the case for breast [28], colorectal and lung cancer [35]. As a result, improvement in patient prognosis and overall survival may be seen.…”

Section: Ivyspring International Publishermentioning

confidence: 99%

“…It was concluded that EGFR was a significant independent determinant of survival and a strong predictor for locoregional relapse [24]. Various other cancers have also been found to harbour EGFR mutations and overexpression such as glioblastoma multiforme [25], lung cancer [26], head and neck squamous cell carcinoma [27], breast [28], colorectal [29] and oesophageal cancers [30] leading to a worse patient prognosis.…”

Section: Ivyspring International Publishermentioning

confidence: 99%

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Overexpression of EGFR in Oral Premalignant Lesions and OSCC and Its Impact on Survival and Recurrence

Mirza¹,

Ali²,

Awan³

et al. 2018

Oncomedicine

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Introduction: Oral squamous cell carcinoma (OSCC) the sixth leading cancer worldwide ranks as the most common cancer in males, and the third most common in females in Pakistan. It is influenced by risk factors which are widely consumed in our population. The epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor that is imperative for cell signalling, growth and differentiation. It is mutated and overexpressed in a variety of cancers, while in OSCC it has been linked to poor patient survival; premalignant to malignant transformation and recurrence. This study investigates the use of EGFR as a prognostic factor for OSCC. Materials and Methods: Premalignant (n=29) and OSCC (n=100) formalin-fixed paraffin-embedded tissues were retrieved from the surgical archives of Aga Khan University Hospital (AKUH). Immunohistochemistry for EGFR overexpression was performed using monoclonal antibody on both groups. EGFR expression was correlated with habits of risk factor consumption, clinicopathologic features and 5-year survival and recurrence. Results: 15/29 premalignant and 67/100 OSCC patients had overexpressed EGFR. The upper/lower lip had the highest EGFR positivity among all premalignant sites of lesion (p=0.041). In OSCC patients, those who had EGFR overexpression had worse 5-year survival (univariate: p=0.048, multivariate: p=0.056) and higher chances of recurrence (univariate: p=0.01, multivariate: p=0.004) as compared to EGFR negative patients. Conclusion: EGFR is a viable candidate for an OSCC prognostic marker since its overexpression leads to poor survival and markedly increases the chances of recurrence.

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Section: Ivyspring International Publishermentioning

confidence: 99%

Section: Ivyspring International Publishermentioning

confidence: 99%

Overexpression of EGFR in Oral Premalignant Lesions and OSCC and Its Impact on Survival and Recurrence

Mirza¹,

Ali²,

Awan³

et al. 2018

Oncomedicine

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“…Cetuximab is a chimeric mAb targeting domain III of HER1 and approved for treatment of colorectal cancers (Table ). Due to its higher HER1binding affinity than TGF and EGF, following receptor binding, phosphorylation will be induced which can potentially lead to modification of biological responses, interfering with aberrant growth signals and/or triggering cell apoptosis . Furthermore, this mAb is capable of other classical antibody‐dependent cell‐mediated cytotoxicity (ADCC) or complement‐dependent cytotoxicity which improve the mAb therapeutic efficacy in treatment of malignant tumours .…”

Section: Anit‐her1 Mabs and Derivativesmentioning

confidence: 99%

“…Due to its higher HER1binding affinity than TGF and EGF, following receptor binding, phosphorylation will be induced [15][16][17][18] which can potentially lead to modification of biological responses, interfering with aberrant growth signals and/or triggering cell apoptosis. [10,19,20] Furthermore, this mAb is capable of other classical antibody-dependent cell-mediated cytotoxicity (ADCC) or complement-dependent cytotoxicity which improve the mAb therapeutic efficacy in treatment of malignant tumours. [21][22][23][24][25] In addition to these, cetuximab is the only effective mAb for relapse or metastatic cancers.…”

Section: Nimotuzumab (Theracim)mentioning

confidence: 99%

Monoclonal antibody-based therapeutics, targeting the epidermal growth factor receptor family: from herceptin to Pan HER

Moradi‐Kalbolandi

Hosseinzade

Salehi

et al. 2018

Journal of Pharmacy and Pharmacology

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Objectives Monoclonal antibody-based of cancer therapy has been considered as one of the most successful therapeutic strategies for both haematologic malignancies and solid tumours in the last two decades. Epidermal growth factor receptor (EGFR) family signalling pathways play a key role in the regulation of cell proliferation, survival and differentiation. Hence, anti-EGFR family mAbs is one of the most promising approaches in cancer therapy. Key findings Here, recent advances in anti-EGFR mAb including approved or successfully tested in preclinical and clinical studies have been reviewed. Although we focus on monoclonal antibodies against the EGF receptor, but the mechanisms underlying the effects of EGFR-specific mAb in cancer therapy, to some extend the resistance to existing anti-EGFR therapies and some therapeutic strategies to overcome resistance such as combination of mAbs on different pathways are briefly discussed as well. Summary The EGFR family receptors, is considered as an attractive target for mAb development to inhibit their consecutive activities in tumour growth and resistance. However, due to resistance mechanisms, the combination therapies may become a good candidate for targeting EGFR family receptors.

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“…A number of techniques including immunohistochemistry (IHC), DNA microarray technology, fluorescent in situ hybridization (FISH) are utilized to reveal molecular differences within the same or different histopathological specimens [14][15][16]. Using IHC and DNA microarrays lead to the identification of five discrete subtypes of breast cancer.…”

Section: Molecular Classificationmentioning

confidence: 99%

Endocrine and Cell Surface Receptor Signaling in Breast Carcinogenesis

Alanazi¹,

Khan²

2018

Breast Cancer and Surgery

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Breast cancer is the most commonly diagnosed cancer and the leading cause of cancerrelated death in female. To better understand the growth and progression as well as therapeutic management, breast cancers are grouped based on histopathological and molecular classification. A number of factors have been implicated in the development of breast cancer. Various cell surface as well as hormone receptor signaling play crucial role in breast cancer initiation and progression. This chapter briefly discusses few of the important receptor signaling pathways and the various strategies in practice as well as at different stages of development to target these pathways.

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Understanding EGFR Signaling in Breast Cancer and Breast Cancer Stem Cells: Overexpression and Therapeutic Implications

Cited by 38 publications

References 67 publications

Overexpression of EGFR in Oral Premalignant Lesions and OSCC and Its Impact on Survival and Recurrence

Overexpression of EGFR in Oral Premalignant Lesions and OSCC and Its Impact on Survival and Recurrence

Monoclonal antibody-based therapeutics, targeting the epidermal growth factor receptor family: from herceptin to Pan HER

Endocrine and Cell Surface Receptor Signaling in Breast Carcinogenesis

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