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Editorial
. 2009 Sep 3;361(10):1018-20.
doi: 10.1056/NEJMe0905763. Epub 2009 Aug 19.

Personalized medicine and inhibition of EGFR signaling in lung cancer

Adi F Gazdar
Editorial

Personalized medicine and inhibition of EGFR signaling in lung cancer

Adi F Gazdar. N Engl J Med. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

Dr. Gazdar reports receiving consulting fees from AstraZeneca, Genentech, and Boehringer Ingelheim. No other potential conflict of interest relevant to this article was reported.

Figures

Figure 1
Figure 1. Targeting the Epidermal Growth Factorb Receptor (EGFR) Signaling Pathway
The family of surface-receptor tyrosine kinases encoded by EGFR consists of four members that form homodimers or heterodimers after ligand binding. Dimerization results in the activation of tyrosine kinases, which is followed by stimulation of three major signaling pathways, eventually leading to the activation of five of the six hallmarks of cancer (with the exception of limitless replication). The classic mutations of the EGFR kinase domain result in ligand-independent activation of the pathway. Tyrosine kinase inhibitors, such as erlotinib and gefitinib, interfere with the kinase activity of the gene and prevent downstream signaling. Activation of EGFR signaling also leads to an autocrine loop resulting from the formation and release of ligands. The ligands require release from their membrane-bound precursor forms by the activity of sheddase proteins. Only nodal points in the pathway are displayed, indicating targets of therapies in current clinical use or in trials (red arrows). Akt denotes protein kinase B, PI3K phosphatidylinositol 3-kinase, PTEN phosphatase and tensin homologue, MAPK mitogen- activated protein kinase, mTOR mammalian target of rapamycin, P phosphorylation, STAT signal transducer and activator of transcription, and TGF-α transforming growth factor α.
See this image and copyright information in PMC

Comment in

  • Treatment of lung cancer.
    Takano T. Takano T. N Engl J Med. 2009 Dec 17;361(25):2485-6; author reply 2486-7. N Engl J Med. 2009. PMID: 20050213 No abstract available.

Comment on

  • Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.
    Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Mok TS, et al. N Engl J Med. 2009 Sep 3;361(10):947-57. doi: 10.1056/NEJMoa0810699. Epub 2009 Aug 19. N Engl J Med. 2009. PMID: 19692680 Clinical Trial.
  • Screening for epidermal growth factor receptor mutations in lung cancer.
    Rosell R, Moran T, Queralt C, Porta R, Cardenal F, Camps C, Majem M, Lopez-Vivanco G, Isla D, Provencio M, Insa A, Massuti B, Gonzalez-Larriba JL, Paz-Ares L, Bover I, Garcia-Campelo R, Moreno MA, Catot S, Rolfo C, Reguart N, Palmero R, Sánchez JM, Bastus R, Mayo C, Bertran-Alamillo J, Molina MA, Sanchez JJ, Taron M; Spanish Lung Cancer Group. Rosell R, et al. N Engl J Med. 2009 Sep 3;361(10):958-67. doi: 10.1056/NEJMoa0904554. Epub 2009 Aug 19. N Engl J Med. 2009. PMID: 19692684

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    1. Mok TS, Wu Y-L, Thongprasert S, et al. Gefitinib or carbo-platin–paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947–57. - PubMed

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