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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
P1.01-038 - Identification and Characterization of Circulating Tumor Cells from Lung Cancer Patients for Selecting Target Anticancer Drugs for Relapse (ID 9926)
09:30 - 16:00 | Presenting Author(s): Bong-Seog Kim
Metastasis was found in most of lung cancer patients resulting in death. Patient-derived xenograft model using tumor tissues and circulating tumor cells provides the opportunity to assess the biological features of cancer repeatedly during the cancer evolution, enabling clinicians to react quickly to treat the patient with the most suitable specific targeted therapy.
For setting up ex vivo culturing CTCs and establishment of patient-derived CTC xenograft model obtained from liquid biopsy of lung cancer patient, we plan to collect liquid biopsy (n>100) samples from each patient either once or several times before and after treatment. This study will be approved by our institutional review board and local ethics committee. All patient agree their informed consent for inclusion in this study. After collecting mononuclear cells, CTCs is isolated. Patient-derived CTC xenograft model will established using ex vivo cultured CTCs. Using both ex vivo cultured CTCs and patient-derived CTC xenograft model, various target anti-cancer drugs will be screened. And we then examined genetic variations and expression profile of CTC cells.
Based on these results, we identify the drugable target somatic mutations and characterizing the biologic behaviors of CTCs cells based on the results of consequence network via activation of somatic mutation. In case of lung cancer cells expressing EGFR mutation at diagnosis, we found that EGFR mutation was existed during chemotherapy. At the stage of metastasis, clonal evolution of lung cancer cells having EGFR mutation was detected. After examining the cytotoxicity of CTC cells by treatment of 3[rd] generation anti-EGRF inhibitor (3 different types) in vitro and in vivo model, we found a set of somatic mutations were we identified a set of somatic mutations associated with relapse and chemoresistance. These somatic mutations were involved in impairing DNA repair and activating EGFR-mediated cell signaling. Since effective anti-cancer drugs could be selected through screening of target anti-cancer drugs in PDX model following by identifying somatic mutation and expression profiles of CTC lung cancer cells, we suggest that our screening biosystem is useful to maintain the status of complete remission.
CTC analysis can support the delivery of precision anticancer treatments, as specific biomarkers of response to targeted drugs can be appraised. Assuming that CTC induces the recurrence and metastasis, isolated CTC isolated from blood of lung cancer patients may have characteristics of cancer stem cells. Subsequently, CTC could be ex vivo cultured and apply to xenograft model to confirm genetic signatures of CTC.