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• 10497

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  P1.01 - Poster Session 1 - Cancer Biology (ID 143)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10518

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    P1.01-021 - Class III beta-tubulin expression in non-small cell lung cancer as a predictive marker for paclitaxel. (ID 2627)

    14:10 - 14:24  |  Author(s): T. Ohashi
    • Abstract

    Background
    Paclitaxel is one of the key drugs used in chemotherapy for the non-small cell lung cancer (NSCLC). Anti-microtubule agents, such as paclitaxel, stabilizes the microtubule polymer and prevents their breakdown. Data from the metastatic study suggest high tumor class III beta-tubulin (TUBB3) expression is a determinant of insensitivity to paclitaxel. To clarify whether TUBB3 is a true predictive marker for chemotherapy with paclitaxel, chemosensitivity was examined using an in vitro drug sensitivity assay.

    Methods
    Initially, 12 specimens were obtained to analyze the dose-response curve and to measure the median effective dose 50 (ED50) in the histoculture drug response assay (HDRA). The HDRA was perfomed for paclitaxel at several concentrations (minimum 0 μg/ml ,maximal 256μg/ml), in order to analyze the dose-response curves for individual patients. The value that was obtained from HDRA were directly applied for non-linear least square analysis using a formula of simplified dose-response curve. Subsequently, 41 surgically resected NSCLC specimens were applied to the HDRA and inhibition ratio at the concentration of 25μg/ml paclitaxel (IR25) was measured. H-scores were calculated by immunohistochemical staining. The patients comprised 26 male patients and 15 female patients. Mean age was 72±6.8. The specimens examined were 24 adenocarcinomas 17 squamous cell carcinomas.

    Results
    The mean (±SD) slope factor, ED50 and maximal response was 11.7±6.5, 24.6±7.73 μg/ml and 87.4±6.15% respectively. And the mean H-score was 50; (20-140). Among 12 specimens whose dose-response curve was obtained, the ED50 was higher than 25μg/ml in 5 (Resistant group) and lower in 7 (Sensitive group). The median H-score was significantly (p=0.0076) higher in Resistant group (240) than in Sensitive group (10). The mean IR25 was 53.8±26.6%. The median H-score in the specimens with IR25 above 50% (60, n=15) was significantly (p=0.0337) higher than that in specimens with IR25 under 50% (35, n=26).

    Conclusion
    Tumors with high TUBB3 levels exhibited chemoresistance to paclitaxel than tumors with low TUBB3 levels. HDRA revealed that TUBB3 expression is a true predictive factor for the response of paclitaxel in NSCLC.