Author of

• 18374

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  P3.02b - Poster Session with Presenters Present (ID 494)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 18412

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    P3.02b-038 - Molecular Dynamics Simulation of EFGR L844V Mutant Sensitive to AZD9291 in Non-Small Cell Lung Cancer (ID 4486)

    14:30 - 14:30  |  Author(s): B. Rashidieh
    • Abstract

    Background:
    The Epidermal growth factor receptor (EGFR) belongs to the ErbB family of Receptors of Tyrosine Kinases (RTK) containing transmembrane domain, an extracellular ligand-binding domain and intracellular region which the tyrosine-kinase region which has activity for signal transduction. EGFR has a critical role in the efficient control of growth, proliferation, survival and differentiation in cells. Approximately half of cases of triple-negative breast cancer (TNBC) and inflammatory breast cancer (IBC) overexpress EGFR. In many other cancers namely, lung and colon cancer the overexpression of this receptor has been observed as well. In more than 60% of non-small cell lung carcinomas (NSCLCs) mutation in EFGR has been occurred, so EGFR also has become an important therapeutic target for the treatment of these tumors. In recent years, designing drugs to inhibit the activity of this receptor in cancer cells has been on the agenda of Precision Medicine Scientists. Such treatment so called targeted therapy is considered as a new approach to treat cancer, in which the treatment is more effective, specific and has fewer side effects for the patient. These drugs are inhibitors that block extracellular protein or impair a part of Tyrosine kinase activity (TKIs). It is essential to note that mutations in EGFR limit the use of these medications; thus, so far three generations of these drugs have been developed to inhibit the Tyrosine kinase activity. The first generations of Tyrosine kinase inhibitors are used in the treatment of patients who have a L858R mutant in EGFR. The second-generation drug could overcome T790M mutation. AZD9291 belongs to third-generation drug and is a potent, selective and irreversible inhibitor of both EGFR sensitizing and T790M resistance mutations with less activity towards wild-type EGFR. This drug overcomes the T790M mutation, in addition to the fact that it can overcome sensitive mutants such as L844V. L844V is a mutation in the drug resistant cells and did not lead to constitutive EGFR phosphorylation.
    
    Methods:
    This study examines how AZD9291 drug interact with EGFR protein kinase in L844V mutant with adopting docking and dynamic molecular simulation using Gromacs software version 4.5.6 to understand how this protein develop sensitive against the mentioned drug.
    
    Results:
    The results of the analysis of RMSD simulation in thirty nanoseconds confirm that the assumptions of the study is correct.
    
    Conclusion:
    AZD9291 as a new inhibitor seem to form a stable interaction with the L844V mutant.