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Susmita Ghosh



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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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      P1.13-33 - Ex Vivo 2*2*2 Tumor Tissue Explant Culture for Precision Medicine in Immunotherapy and TKI progressors in Lung Cancer (ID 14085)

      16:45 - 18:00  |  Author(s): Susmita Ghosh

      • Abstract
      • Slides

      Background

      Lung cancer is one of the leading causes of cancer mortality worldwide. Despite of remarkable progress made in the lung cancer therapy, an unmet need is there in tailoring the appropriate patient specific therapy due to a variety of treatment options. Our aim was to develop a high-throughput drug screening method of tumor ex-vivo analysis (TEVA) which can predict patient-specific drug response and thus can be used for personalized cancer treatment.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Freshly operated tumor tissue samples from non small cell lung carcinoma (NSCLC) patients were received from Soroka Medical Center, Israel and implanted in NSG mice to form PDXs. We developed a method that enabled us to cut the PDXs into 2*2*2mm tissue explants and then treated with clinically relevant drugs (Genomics/proteomics suggested) in 48 well plates for 24 hours. TMA blocks were prepared and IHC was performed. Parameters, such as Ki67, TUNEL and respective signalling molecules (pMAPK, pPRAS40) were chosen to predict the drug response ex vivo and a score was given to each drug based upon those parameters.

      4c3880bb027f159e801041b1021e88e8 Result

      8 NSCLC patients have been enrolled so far. Implantation rate was 75%. 15 drugs combinations have been developed to test the most common conditions, i.e. progression on EGFR TKIs, progression on immunotherapy and progression on chemotherapy. Preliminary results indicate a potential role for MET blockade in immune-resistant as well as in EGFR progressors. We also observed that the TEVA score correlated with the genomics/proteomics based drug results.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Overall, this low cost, fast, relatively simple and efficient method can bypass the necessity of drug validation in mice and can be used for multiple drug screening to select a precise patient specific drug. The method is feasible and expose ways to overcome acquired resistant to novel drugs.

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