肺癌的诊断治疗进展.pptVIP

* * ADDITIONAL INFORMATION KEY POINT: * Computer-Generated Tri-Dimensional Structure of the EGFR-ATP Binding Site In the above picture the inhibitor gefitinib occupies the adenosine triphosphate (ATP) cleft The two missense mutations are shown within the activating loop of the tyrosine kinase The three in-frame deletions are all present within another loop which flanks the ATP cleft Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350:2129-2139. * A number of different techniques have been employed to investigate the molecular characteristics of NSCLC tumors from patients participating in clinical trials testing EGFR TKIs. Techniques currently used to identify EGFR mutation status, gene copy number, and protein expression include gene sequencing, fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC), respectively. All these techniques require the use of patient tumor tissue. Gene sequencing can be performed by different methods, including DNA polymerase chain reaction (PCR) and RNA reverse transcription PCR. Such techniques can help identify abnormal EGFR DNA sequences within the genome of the tumor cells. FISH analysis measures fluorescent-labeled probes hybridized to specific gene sequences within a cell. Gene amplification can be determined effectively by fluorescence microscopy visualization. FISH results are a quantitative score of the level of gene amplification. IHC is a method of identifying the presence of a protein in cells or tissues via specific antibodies. IHC staining is a qualitative approach to detect protein expression levels. * * Pre-specified analyses in the statistical analysis plan for study BR.21 included stratifications on the basis of performance status, prior therapy (including platinum therapy), responsiveness to prior therapy, and HER1/EGFR status. Treatment of NSCLC