Structural analysis of the EGFR TK domain and potential implications for EGFR targeted therapy

  • Authors:
    • Weiwei Nie
    • Lin Tang
    • Haiyang Zhang
    • Jiaqing Shao
    • Yucai Wang
    • Longbang Chen
    • Donghai Li
    • Xiaoxiang Guan
  • View Affiliations

  • Published online on: February 3, 2012     https://doi.org/10.3892/ijo.2012.1356
  • Pages: 1763-1769
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The development and clinical application of TK domain inhibitors (TKIs) provide important insights into the broader field of cancer-targeted therapies. To discuss the recent advances in the atomic level understanding of EGFR TK domain mutations, we aim at highlighting the current and future importance of these studies on malignancies where the TK domain is improperly activated. The analysis is conducted on published TK domain crystal structures deposited in the Protein Data Bank, or homology structures generated by homology modeling and AutoDock 4.2 software using the program O. Mutations in exon 19 are the most common pathogenic mutations, so the crystal structures with these mutations are analyzed and compared in detail. In addition, we demonstrate how these crystal structures of EGFR conformation with TK domain mutations and those binding with small molecule inhibitors unveil the active or inactive mechanisms. As to the increasing resistance to the TKI, we summarize the progress on overcoming this challenge. Simultaneously, we predict the structure of BIKW-2992 binding to EGFR and compare it with the validated structure of HKI-272. It is hoped that a more accurate resistance mechanism would be found. In brief, we believe that this research will provide insights into EGFR targeted therapies.

Related Articles

Journal Cover

June 2012
Volume 40 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Nie W, Tang L, Zhang H, Shao J, Wang Y, Chen L, Li D and Guan X: Structural analysis of the EGFR TK domain and potential implications for EGFR targeted therapy. Int J Oncol 40: 1763-1769, 2012
APA
Nie, W., Tang, L., Zhang, H., Shao, J., Wang, Y., Chen, L. ... Guan, X. (2012). Structural analysis of the EGFR TK domain and potential implications for EGFR targeted therapy. International Journal of Oncology, 40, 1763-1769. https://doi.org/10.3892/ijo.2012.1356
MLA
Nie, W., Tang, L., Zhang, H., Shao, J., Wang, Y., Chen, L., Li, D., Guan, X."Structural analysis of the EGFR TK domain and potential implications for EGFR targeted therapy". International Journal of Oncology 40.6 (2012): 1763-1769.
Chicago
Nie, W., Tang, L., Zhang, H., Shao, J., Wang, Y., Chen, L., Li, D., Guan, X."Structural analysis of the EGFR TK domain and potential implications for EGFR targeted therapy". International Journal of Oncology 40, no. 6 (2012): 1763-1769. https://doi.org/10.3892/ijo.2012.1356