The Role of EGFR Inhibition in the Treatment of Non-Small Cell Lung Cancer

Ray, Mandira; Salgia, Ravi; Vokes, Everett E.

doi:10.1634/theoncologist.2009-0054

Cited by 55 publications

(44 citation statements)

References 123 publications

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“…Overexpression of EGFR has been implicated in greater than 60% of NSCLC patients. NSCLC cell lines also produce EGFR ligands, EGF and transforming growth factor-alpha, which bind to the EGFR receptors in an autocrine fashion, resulting in cell proliferation and gene transcription [3]. EGFR mediates these cellular responses via several downstream signaling pathways, including the PI3K/Akt and the MAPK pathways [26].…”

Section: Egfr: Structure Targeted Pathways and Dysregulation In Cancermentioning

confidence: 99%

“…The most common therapies targeting EGFR and c-Met are kinase inhibitors and MAbs [3,41]. TKIs are small-molecule kinase inhibitors that bind to the intracellular domain of RTKs and inhibit their function.…”

Section: Egfr and C-met As Therapeutic Targets: Agents Targeting Egfrmentioning

confidence: 99%

“…Erlotinib and gefitinib are reversible TKIs, which have been approved for the treatment of NSCLC patients [3]. Lapatinib is a dual kinase inhibitor that targets EGFR, as well as the HER2 receptor [45].…”

Section: Egfr Tkis and Mabsmentioning

confidence: 99%

“…Human epidermal growth factor receptor (EGFR) and c-Met are receptor tyrosine kinases (RTKs) that are encoded by genes located on the short arm of chromosome 7 [3,4]. Both RTKs have an extracellular ligand binding domain, a transmembrane portion, and a tyrosine kinase moiety, located intracellularly [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, c-Met is activated by a single ligand, known as hepatocyte growth factor/scatter factor (HGF), which is secreted by fibroblasts, smooth muscle cells, and other mesenchymal cells [4]. Stimulation of EGFR and c-Met, by binding of their corresponding ligands, results in autophosphorylation of the tyrosine kinase domains, which causes downstream signaling and further activation of the mitogen-activated protein kinase (MAPK), RAS-RAF-MEK-ERK/MAPK, and phosphatidylinositol 3-kinase (PI3K)/Akt pathways [3,7] (Figure 1). Under physiological conditions, the PI3K/Akt and MAPK pathways are involved in diverse cellular processes, such as angiogenesis, metabolism, growth, proliferation, survival, protein synthesis, transcription, apoptosis [8], differentiation, organism development, and cell cycle regulation and progression [9,10].…”

Section: Introductionmentioning

confidence: 99%

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EGFR and c-Met Inhibitors are Effective in Reducing Tumorigenicity in Cancer

Stone¹,

Harrington²,

Frakes³

et al. 2014

J Carcinog & Mutagen

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EGFR and c-Met are receptor tyrosine kinases that are implicated in tumor development and progression in several types of cancer. Both EGFR and c-Met, which are known to be overexpressed and mutated in cancer, share common signaling pathways, including the PI3K/ Akt and MAPK pathways. Small molecule tyrosine kinase inhibitors and monoclonal antibodies that work against EGFR and c-Met are at the forefront of cancer therapy, but their individual efficacies are limited due to the development of drug resistance. In recent pre-clinical studies, we observed that combination therapy using mTOR and Wnt inhibitors with EGFR or c-Met tyrosine kinase inhibitors resulted in overcoming drug resistance. Our studies also indicated that EGFR and c-Met tyrosine kinase inhibitor resistance may be due to activation of alternative signaling pathways. The development of additional combinatorial therapies is underway, and various combinations of inhibitors have shown promising results in clinical trials. Future studies in this direction could be the basis for development of new cancer therapeutics, utilizing EGFR and c-Met inhibitors, which could greatly improve patient prognosis.

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Section: Egfr: Structure Targeted Pathways and Dysregulation In Cancermentioning

confidence: 99%

Section: Egfr and C-met As Therapeutic Targets: Agents Targeting Egfrmentioning

confidence: 99%

Section: Egfr Tkis and Mabsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

EGFR and c-Met Inhibitors are Effective in Reducing Tumorigenicity in Cancer

Stone¹,

Harrington²,

Frakes³

et al. 2014

J Carcinog & Mutagen

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Targeting EGFR‐mediated autophagy as a potential strategy for cancer therapy

Sooro

Zhang

2018

Intl Journal of Cancer

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Autophagy is a naturally occurring programed cellular catabolic process stimulated by cellular stress for energy homeostasis maintenance and elimination of harmful substances. It mostly works as pro-survival mechanism but on the other hand deregulation of autophagy has been linked to non-apoptotic cell death known as "type II programed cell death." Emerging evidences indicate that EGFR (epidermal growth factor receptor)-mediated RAS/RAF/MEK/ERK signaling pathway plays a critical role in the induction of autophagy in various tumors. It has further been established that this signaling pathway is also involved in several other anti-proliferative events such as apoptosis and senescence. However, the signaling pathway activity and effects are highly dependent on the cell type and the stimulus. It is currently being evident that autophagy induction by RAS/RAF/MEK/ERK pathway through small molecules may be a potential therapeutic strategy for cancer. However, to our best knowledge, the role of EGFR-mediated RAS/RAF/MEK/ERK signaling pathway in autophagy-mediated cell death and survival have not previously been reviewed. In this review, we discuss the current state of knowledge on how RAS/RAF/MEK/ERK signaling pathway regulates autophagy and the role of this EGFR-mediated autophagy in diseases. We further examine the cross-talk between this EGFR-mediated autophagy and apoptosis as well as how this process is currently being utilized for cancer treatment and suggest promoting autophagy-related cell death by small molecules may be exploited to design better therapeutic strategies for early stage and locally advanced tumors.

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Predictive Markers in Lung Cancer

Liu¹,

Gitlitz²

2012

Biomarkers in Oncology

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The Role of EGFR Inhibition in the Treatment of Non-Small Cell Lung Cancer

Cited by 55 publications

References 123 publications

EGFR and c-Met Inhibitors are Effective in Reducing Tumorigenicity in Cancer

EGFR and c-Met Inhibitors are Effective in Reducing Tumorigenicity in Cancer

Targeting EGFR‐mediated autophagy as a potential strategy for cancer therapy

Predictive Markers in Lung Cancer

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