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Ka-Won Noh

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    P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.13-04 - Integrin β3 Inhibition Enhances the Antitumor Activity of ALK Inhibitor in ALK Rearranged NSCLC (ID 12325)

      16:45 - 18:00  |  Author(s): Ka-Won Noh

      • Abstract


      Anaplastic lymphoma kinase (ALK)-positive cancers are sensitive to small molecule ALK kinase inhibitors, but most cases experience failure following treatment. Hence, additional drug targets and combination therapeutic treatments are needed. We investigated gene expression that is regulated by the expression of ALK and explored its roles in cancer progression and therapeutic implication.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We screened ALK-rearranged non-small cell lung cancer (NSCLC) cases using immunohistochemistry and fluorescence in situ hybridization, and then conducted multiplex gene expression analysis. We also performed a clinicopathological analysis to validate the findings. Additional cellular experiments, including inhibition and migration assays, and in vivo lung cancer model studies were performed.

      4c3880bb027f159e801041b1021e88e8 Result

      Among patients with ALK-rearranged NSCLC, integrin β3 (ITGB3) was one of the overexpressed genes in comparison with that in ALK-negative NSCLC (P = 0.0003). ALK and integrin β3 expression were positively correlated, and we discovered that high integrin β3 mRNA expression was associated with metastasis and more advanced tumor stages (P <0.005; P < 0.05). Furthermore, we found that inhibition of both ALK and integrin β3 led to increased drug sensitivity in vitro and in vivo (both P < 0.05).

      8eea62084ca7e541d918e823422bd82e Conclusion

      We discovered a positive correlation between ALK and integrin β3 expression levels in ALKrearranged NSCLC. Our findings suggest that high integrin β3 expression in ALK-rearranged NSCLC is associated with tumor progression and a worse prognosis. This demonstrates the prognostic value of integrin β3 and provides a rationale for combination treatment with ALK and integrin β3 inhibitors in patients with ALK-rearranged NSCLC.