Epidermal Growth Factor Receptor Inhibitors in the Treatment of Non-small Cell Lung Cancer

Wheatley‐Price, Paul; Shepherd, Frances A.

doi:10.1007/978-1-60761-524-8_10

Cited by 3 publications

(2 citation statements)

References 112 publications

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“…Ligands for these receptors, most importantly epidermal growth factor (EGF) and transforming growth factor- α (TGF- α ), bind to the extracellular domain resulting in receptor dimerization and autophosphorylation of the intracellular receptor tyrosine kinase (RTK) domain, leading to downstream signaling, including the activation of ras , raf , mitogen-activated protein kinase (MAPK), phosphatidyl-3 kinase (PI3K/Akt), and ERK1/2. These molecules are linked to cell growth, proliferation, motility, and survival [ 28 ]. Previous studies revealed that EGFR is activated (phosphorylated) in a dose- and time-dependent manner when exposed to CS solution [ 29 ].…”

Section: Resultsmentioning

confidence: 99%

“…The prolonged activation of EGFR is accompanied by activation of Ras, the downstream survival, and proliferative signaling molecules Akt and ERK1/2, as well as the transcription factors c-Myc and c-Fos. Given that more than 80% of CS-induced nonsmall cell lung carcinomas (NSCLCs) express EGFR [ 2 ], inhibition of EGFR has become an important therapeutic target for the treatment of these tumors [ 28 , 57 , 58 ]. We have demonstrated that both anti-p-BQ antibody and vitamin C prevent AECS/p-BQ-induced activation of EGFR and proliferation of lung cells ( Figure 12 ).…”

Section: Discussionmentioning

confidence: 99%

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Molecular Mechanisms of Cigarette Smoke-Induced Proliferation of Lung Cells and Prevention by Vitamin C

Dey

Chattopadhyay²,

Chatterjee³

2011

Journal of Oncology

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Lung cancer is the leading cause of cancer dearth. Cigarette smoking is the strongest risk factor for developing lung cancer, which is conceivably initiated by proliferation. Here, we show that low concentration of aqueous extract of cigarette smoke (AECS) causes excessive proliferation of human lung epithelial cells (A549) without any apoptotic cell death. The causative factor responsible for AECS-induced proliferation has been identified as p-benzoquinone (p-BQ). Coimmunoprecipitation and immunoblot experiments indicate that p-BQ binds with epidermal growth factor receptor (EGFR). However, in contrast to EGF, it causes aberrant phosphorylation of EGFR that lacks c-Cbl-mediated ubiquitination and degradation resulting in persistent activation of EGFR. This is followed by activation of Hras + Kras and the downstream survival and proliferative signaling molecules Akt and ERK1/2, as well as the nuclear transcription factors c-Myc and c-Fos. Vitamin C and/or antibody to p-BQ prevents AECS/p-BQ-induced proliferation of lung cells apparently by inactivating p-BQ and thereby preventing activation of EGFR and the downstream signaling molecules. The results suggest that vitamin C and/or antibody to p-BQ may provide a novel intervention for preventing initiation of lung cancer in smokers.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Molecular Mechanisms of Cigarette Smoke-Induced Proliferation of Lung Cells and Prevention by Vitamin C

Dey

Chattopadhyay²,

Chatterjee³

2011

Journal of Oncology

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The one year survival rate of lung adenocarcinoma patients treated with chemotherapy or targeted therapy

et al. 2020

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Recent Advances in Epidermal Growth Factor Receptor Inhibitors (EGFRIs) and their Role in the Treatment of Cancer: A Review

Unnisa

Chettupalli

Hussain

et al. 2022

ACAMC

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Tyrosine kinases are known to play a role in tumour growth and proliferation, and they have become common drug targets. Tyrosine kinase inhibitors (TKIs) prohibit associated kinases from phosphorylating tyrosine residues in their substrates, preventing downstream signaling pathways from being activated. Multiple robust and well-tolerated TKIs targeting single or multiple targets, including EGFR, ALK, ROS1, HER2, NTRK, VEGFR, RET, MET, MEK, FGFR, PDGFR, and KIT, have been developed over the last two decades, contributing to our understanding of precision cancer medicine based on a patient's genetic alteration profile. The epidermal growth factor receptor (EGFR) family consists of four transmembrane tyrosine kinases (EGFR1/ErbB1, Her2/ErbB2, Her3/ErbB3, and Her4/ErbB4) and thirteen polypeptide ligands produced by them. Multiple solid tumours, including breast, pancreatic, head and neck, kidney, vaginal, renal, colon, and non-small cell lung cancer, overexpress EGFRs. Overexpression of these genes stimulates downstream signaling channels, causing cell proliferation, differentiation, cell cycle progression, angiogenesis, cell motility, and apoptosis inhibition. EGFRs' high expression and/or adaptive activation coincides with the pathogenesis and development of many tumours, making them appealing candidates for both diagnosis and therapy. Several strategies for targeting these receptors and/or the EGFR-mediated effects in cancer cells have been established. The majority of methods include the development of anti-EGFR antibodies and/or small-molecule EGFR inhibitors. This review presents the recent advances in EGFR TKIs and their role in the treatment of cancer.

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Epidermal Growth Factor Receptor Inhibitors in the Treatment of Non-small Cell Lung Cancer

Cited by 3 publications

References 112 publications

Molecular Mechanisms of Cigarette Smoke-Induced Proliferation of Lung Cells and Prevention by Vitamin C

Molecular Mechanisms of Cigarette Smoke-Induced Proliferation of Lung Cells and Prevention by Vitamin C

The one year survival rate of lung adenocarcinoma patients treated with chemotherapy or targeted therapy

Recent Advances in Epidermal Growth Factor Receptor Inhibitors (EGFRIs) and their Role in the Treatment of Cancer: A Review

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