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Review
. 2016 Dec;5(12):3572-3578.
doi: 10.1002/cam4.944. Epub 2016 Oct 21.

Epidermal growth factor receptor and notch signaling in non-small-cell lung cancer

Joanna Pancewicz-Wojtkiewicz  1
Affiliations
Review

Epidermal growth factor receptor and notch signaling in non-small-cell lung cancer

Joanna Pancewicz-Wojtkiewicz. Cancer Med. 2016 Dec.

Abstract

Lung cancer is the most common reason of cancer deaths and about 85% of these are non-small-cell lung cancer. Currently, lung cancer therapy is mainly based on the tumor node metastasis (TNM) disease staging and tumor histological classification. Despite therapeutic innovations, the prognosis for lung cancer patients has not significantly changed in the last years. Therefore, a proper understanding of cell signaling pathways involved in cancer pathogenesis seems to be essential for improvement in cancer therapy field. The knowledge of crosstalk between epidermal growth factor receptor (EGFR) and Notch pathway can lead to enhanced screening for the expression of these genes allowing patients to optimize treatment options and predict potential treatment resistance. This review focuses on recent advances related to the mechanisms of EGFR and Notch signaling in non-small-cell lung cancer and the effectiveness of current Notch- and EGFR-targeted therapies.

Keywords: Epidermal growth factor receptor; Notch; non-small-cell lung cancer; tyrosine kinase inhibitors.

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Figures

Figure 1
Figure 1
The scheme shows that activation of EGFR triggers PI3K/AKT/mTOR pathways cascade, which increases the translation of hypoxia‐inducible factors. Moreover, hypoxia can stabilize NICD by interaction with HIF‐1α. TKISs, tyrosine kinase inhibitors; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; PI3K/AKT, phosphatidylinositide 3‐kinases; mTOR, mechanistic target of rapamycin; NICD, intracellular domain of Notch; HIF‐1α, hypoxia‐inducible factors.
Figure 2
Figure 2
Possible mechanisms of crosstalk between EGFR and Notch and clinical consequences: (A) EGFR cooperates with intracellular domain of Notch by enhancing its effect on tumor apoptosis, (B) EGFR overexpression downregulates Notch, (C) Notch upregulates EGFR expression through p53 as a mediator of the Notch‐1. NICD, intracellular domain of Notch.
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