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H. Mizuuchi



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    P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.06-033 - Identification f IGF-1R activation as a candidate molecular target in KRAS-mutated lung cancer (ID 2519)

      09:30 - 09:30  |  Author(s): H. Mizuuchi

      • Abstract

      Background
      KRAS mutations are common driver mutations in 30% of non-small cell lung cancer. However, treatment for lung cancer patients with KRAS mutations remains unestablished. Therefore, to screen other targetable receptor tyrosine kinases (RTKs) in lung cancers with KRAS mutations, we performed phospho-RTK array analyses using 6 KRAS mutated lung cancer cell lines.

      Methods
      Sixteen NSCLC cell lines were analyzed using Human-Phospho-RTK Array Kit (R&D Systems, MN) and relative phosphorylation levels of 42 RTKs were examined. Phosphorylation levels of RTKs were quantified relative to the average of positive controls using image analysis software JustTLC (Sweday, Lund, Sweden). We also examined growth inhibitory effect of small interfering RNA (siRNA) and erlotinib in KRAS mutant lung cancer cell lines. In addition, we developed erlotinib-resistant cell lines from erlotinib-sensitive H358 cells by chronic drug exposure for 3 months.

      Results
      In the phospho-RTK array analysis, phosphorylation levels of EGFR were lowest in the cell lines with KRAS mutation (Table1). Three of six cell lines with KRAS mutation showed IGF-1R phosphorylation and the difference was statistically significant compared with 0 of ten cell lines without KRAS mutation (P=0.03, Fisher's Exact test). KRAS siRNA did not induce apoptosis in 5 cell lines with KRAS mutation but mild apoptosis in H358 cells. Moreover, only H358 showed mild sensitivity to erlotinib (IC~50~ 120nmol/L). Analysis for erlotinib-resistant H358 cells identified increased phosphorylation of IGF-1R compared with H358 parent cells (18.0 times).Figure 1

      Conclusion
      These results suggest IGF-1R may be a candidate molecular target in lung cancers with KRAS mutation.