Egfr, also known as the epidermal growth factor receptor, belongs to the ERBB family of tyrosine kinase receptors. Its signaling cascade is a key regulator in cell proliferation, differentiation, division, survival, and is associated with cancer development [1]. The activation of Egfr leads to autophosphorylation of receptor tyrosine kinase, initiating downstream signaling pathways involved in regulating cellular functions [5].

In non-small cell lung cancer (NSCLC), Egfr mutations are the second most common oncogenic driver event. Classical activating mutations like exon 19 deletions and the L858R point mutation are strong predictors for a good clinical response to Egfr tyrosine kinase inhibitors (Egfri). However, low-frequency mutations within exons 18-25 of the Egfr gene in NSCLC are associated with poorer responses to Egfri [2]. Moreover, in cancer, inappropriate activation of Egfr mainly results from amplification and point mutations at the genomic locus, transcriptional upregulation, or ligand overproduction [3]. Additionally, in NSCLC patients, resistance to tyrosine kinase inhibitors (TKIs) can occur through two central mechanisms: Egfr secondary mutations and bypass signaling activations [4].

In conclusion, Egfr is crucial in regulating normal cellular processes and is significantly involved in cancer development, especially in NSCLC. The study of Egfr in mouse models, though not explicitly detailed in the provided references, would likely further clarify its role in normal biology and disease. Understanding the functions of Egfr and its mutations in NSCLC can potentially lead to the development of more effective treatment strategies for patients with this disease.

References:

1. Sabbah, Dima A, Hajjo, Rima, Sweidan, Kamal. . Review on Epidermal Growth Factor Receptor (EGFR) Structure, Signaling Pathways, Interactions, and Recent Updates of EGFR Inhibitors. In Current topics in medicinal chemistry, 20, 815-834. doi:10.2174/1568026620666200303123102. https://pubmed.ncbi.nlm.nih.gov/32124699/

2. Harrison, Peter T, Vyse, Simon, Huang, Paul H. 2019. Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer. In Seminars in cancer biology, 61, 167-179. doi:10.1016/j.semcancer.2019.09.015. https://pubmed.ncbi.nlm.nih.gov/31562956/

3. Sigismund, Sara, Avanzato, Daniele, Lanzetti, Letizia. 2017. Emerging functions of the EGFR in cancer. In Molecular oncology, 12, 3-20. doi:10.1002/1878-0261.12155. https://pubmed.ncbi.nlm.nih.gov/29124875/

4. Liu, Qian, Yu, Shengnan, Zhao, Weiheng, Chu, Qian, Wu, Kongming. 2018. EGFR-TKIs resistance via EGFR-independent signaling pathways. In Molecular cancer, 17, 53. doi:10.1186/s12943-018-0793-1. https://pubmed.ncbi.nlm.nih.gov/29455669/

5. Singh, Davinder, Attri, Bhupinder Kumar, Gill, Rupinder Kaur, Bariwal, Jitender. . Review on EGFR Inhibitors: Critical Updates. In Mini reviews in medicinal chemistry, 16, 1134-66. doi:. https://pubmed.ncbi.nlm.nih.gov/26996617/