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Hyun Chang
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P3.03 - Chemotherapy/Targeted Therapy (ID 719)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.03-021 - In Vitro Pharmacogenomic Platform with a High-Purity Patient-Derived Cell Model (ID 9850)
09:30 - 09:30 | Presenting Author(s): Hyun Chang
- Abstract
Background:
We have developed a high-purity patient-derived cell (HP-PDC) method for primary culture of malignant effusions from non-small cell lung cancer (NSCLC) patients with oncogenic driver mutations. We updated the results of HP-PDC with mutation test and drug response.
Method:
HP-PDCs were established by a multistep isolation protocol. Malignant effusions were cultured and examined with a light microscope to identify spheroid-forming cells. Immunofluorescence (IF) and flow cytometry were used to evaluate the purity of tumor cell in PDCs. EGFR, ALK or ROS mutation of PDCs was analyzed with direct or PCR-based sequencing and RT-PCR. The sensitivity of target agent to HP-PDCs were tested using a cell viability assay.
Result:
Consecutive series of 79 malignant effusion samples was collected from 61 patients with advanced NSCLC. Spheroid-forming cells were detected in 41 samples which were cultured in AR5 media to establish PDCs. IF analysis revealed that TTF-1 was upregulated in 17 PDCs (21.5%), which also showed EpCAM-positive cell population in flow cytometry with high purity of over 70%. Time spent for establishment of HP-PDCs ranged from 26 days to 132 days. There were 9 PDCs (53%) which harbored active EGFR mutations. Three PDCs with ALK fusion and four with ROS1 fusion were established. Twelve PDC cases were from patients who experienced disease progression while on treatment with EGFR- (9) and ALK- (3) tyrosine kinase inhibitors. Four PDCs with ROS1 fusion were obtained before anti-cancer treatment. Three of PDCs with EGFR mutations were established from patients, who progressed on both gefitinib and the 3[rd] generation EGFR inhibitors. All of them showed in vitro resistance to both gefitinib and 3[rd] generation EGFR inhibitors. PDC from a patient with ROS1 fusion was sensitive to ROS1 inhibitors (entrectinib, crizotinib and ceritinib) in vitro test. The patient has been treated with entrectinib and showed partial response.
Conclusion:
HP-PDCs provide useful in vitro platforms of preclinical studies which predicts responses to targeted therapies in a short period of time and may provide an excellent platform for personalized therapies in NSCLC patients.
