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Eisuke Kurihara



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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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      P1.13-13 - Potent Anti-Tumor Effect of Ganetespib in Acquired EGFR-TKI Resistance NSCLC Cells (ID 12652)

      16:45 - 18:00  |  Presenting Author(s): Eisuke Kurihara

      • Abstract

      Background

      Non-small cell lung cancer (NCSLC) harboring epidermal growth factor receptor (EGFR) mutation shows favorable response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, almost all these patients eventually acquire resistance to EGFR-TKIs, and novel therapeutic strategies to overcome the acquired resistance have been required. The 90-kDa heat shock protein (HSP90) is a chaperon protein expressed at high levels in cancer cells and involved in folding or stabilization of client proteins essential for cancer cell growth and survival. Ganetespib (STA-9090) is one of the second-generation HSP90 inhibitors with potent anti-tumor effect on NSCLC cells. In this study, we evaluated the anti-tumor effect of ganetespib in EGFR-TKI sensitive and acquired resistance NSCLC cell lines.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We treated 4 EGFR-mutant NSCLC cell lines (HCC827, HCC4006, HCC4011 and PC-9), and 5 experimentally established EGFR-TKI (gefitinib) resistance cell lines with ganetespib. The EGFR-TKI resistant mechanism consisted of EGFR T790M second mutation, MET amplification, epithelial-to-mesenchymal transition (EMT) and cancer stem cell-like properties. We determined cell proliferation by MTS assay and calculated the IC50 values. We also performed Western blotting to investigate downstream signaling pathway alterations.

      4c3880bb027f159e801041b1021e88e8 Result

      The IC50 values in parental NSCLC cell lines ranged from 1.3nM to 15nM, and those in acquired EGFR-TKI resistance NSCLC cell lines ranged from 0.87nM to 25nM, which suggests potent anti-tumor effect of ganetespib. In addition, this effect was observed regardless of the resistant mechanisms, including EMT. Ganetespib effectively suppressed the expression of downstream pathway molecules in all examined cell lines including acquired EGFR-TKI resistance NSCLC cell lines. Also, ganetespib effectively induced apoptosis in parental and acquired EGFR-TKI resistance NSCLC cell lines with EGFR T790M mutation or MET amplification.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Ganetespib exhibited potent anti-tumor effect in acquired EGFR-TKI resistance NSCLC cell lines regardless of the resistant mechanisms, suggesting that ganetespib could be a promising therapeutic option in the treatment of NSCLC with acquired EGFR-TKI resistance.

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    P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.01-72 - Pulmonary Resection in a Prone Position for Lung Cancer Invading the Spine: Two Cases Report (ID 12700)

      12:00 - 13:30  |  Author(s): Eisuke Kurihara

      • Abstract

      Background

      The prone position is usually not selected for pulmonary resection. The intraoperative body position is an important issue in surgery for non-small cell lung cancer (NSCLC) invading the spine because the standard intraoperative body position for vertebrectomy is a prone position, while that for pulmonary resection is a lateral decubitus position. Intraoperative changes in body position are correlated with disadvantages such as the risks of infection and nerve injury.

      We have previously reported significantly favorable clinical outcome of induction chemoradiotherapy (iCRT) followed by surgery among patients with clinical T3 or T4 locally advanced NSCLC, compared with initial surgery. iCRT can prevent cancer cell microresidues at local sites and to eradicate micrometastatic disease at distant sites.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Case 1: A 60-year-old man was found to have squamous cell carcinoma of the left lung with invasion of the adjacent chest wall and vertebral bodies from Th3 to Th5 and his clinical stage (UICC 7th edition) was diagnosed as c-stage IIIA (cT4N0M0).

      Case 2: A 63-year-old man was found to have adenocarcinoma of the right lung with invasion of the adjacent chest wall and Th3 and Th4 vertebral bodies and was diagnosed as c-stage IIIA (cT4N1M0).

      They were treated with iCRT consisting of two cycles of cisplatin plus docetaxel with concurrent radiotherapy of total 46 Gy.

      4c3880bb027f159e801041b1021e88e8 Result

      They obtained a moderate decrease in tumor size after iCRT (restaging ycT4N0M0: Case 1, ycT4N0M0: Case 2).

      The surgery was started in the prone position. After partial vertebrectomy and chest wall resection were performed using an O-arm with a navigation system, upper lobectomy with systemic lymph node dissection (sLND) was performed through the chest wall defect via the posterior approach. Firstly, all pulmonary arterial branches to upper lobe were divided. Next, after division of the posterior and anterior interlobar fissure, the upper lobe bronchus was transected. Finally, the upper pulmonary vein was divided, and sLND was performed under an excellent view.

      Pathologic examination confirmed complete resection of squamous cell carcinoma invading the vertebral bodies and a diagnosis of Ef3 and ypN0 in Case 1, and complete resection of adenocarcinoma adjacent to the vertebral bodies, which had not been infiltrated, and a diagnosis of Ef2 and ypN0 in Case 2.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Lobectomy with systemic LND in the prone position, especially after wide resection of the bony thorax, can be performed via the posterior approach without any significant difficulties in the patients with NSCLC invading the spine.

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