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Seung Hyeun Lee
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P53 - Tumor Biology and Systems Biology - Basic and Translational Science - Misc. Topics (ID 213)
- Event: WCLC 2020
- Type: Posters
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P53.01 - Triptolide Enhances Radiosensitivity of Lung Cancer Cells via G2/M Arrest, and Autophage (ID 2421)
00:00 - 00:00 | Presenting Author(s): Seung Hyeun Lee
- Abstract
Introduction
Triptolide is a diterpenoid triepoxide derived from the Chinese herb Tripterygium wilfordii that has been used as a natural medicine in East Asia for hundreds of years. It has various pharmacologic effects including anti-inflammation, anti-oxidant, and anti-cancer activities. However, the radiosensitizing effect of triptolide has scarcely been investigated. Thus we explored the effect and underlying molecular mechanisms in combined triptolide and radiotherapy using lung cancer cells.
Methods
Colony formation assays were conducted to test the radiosensitizing effect of triptolide in lung cancer cell lines (A549 and H460). To determine how triptolide enhances the radiosensitivity, we investigated the immunofluorescence cytometric analysis of apoptosis, western blot analysis for pro-apoptotic signaling pathways, cell cycle analysis, and change in autophage after treatment with fixed dose of triptolide and/or irradiation (1, 2, 3, or 4 Gy).
Results
Combined triptolide and irradiation significantly decreased the surviving fractions than irradiation alone in both cell lines with sensitizing enhancement ratio of 1.56 and 1.51, respectively. Annexin V staining showed that the combination treatment increased apoptosis. The PARP and caspase-3 cleavage, and cytochrome C, bax, and bcl-2 expressions were also more prominent in combination treatment. In addition, cell cycle analysis showed increased G2/M cell cycle arrest in triptolide combination. LC3B overexpression was also observed suggesting autophage may be involved in the cell death in triptolide and irradiation combination.
Conclusion
Triptolide enhanced radiosensitivity of lung cancer cells via apoptosis, cell cycle arrest, and autophage. Although further studies are essentially needed, our data suggest that triptolide may be a candidate radiosensitizer for the treatment of lung cancer.
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P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P76.56 - High PD-L1 Expression is Aassociated with Unfavorable Clinical Outcome in EGFR-Mutated Lung Adenocarcinomas Treated with Targeted Therapy (ID 3152)
00:00 - 00:00 | Presenting Author(s): Seung Hyeun Lee
- Abstract
Introduction
Although programmed death-ligand 1 (PD-L1) expression is widely accepted as a predictive and prognostic biomarker in immunotherapy, its implications in lung cancer patients with driving mutations are still unclear. The objective of this study is to determine the association between PD-L1 expression and treatment outcome in epidermal growth factor receptor (EGFR)-mutated lung cancer treated with tyrosine kinase inhibitors (TKIs).
Methods
We retrospectively enrolled EGFR-mutant, advanced lung adenocarcinoma patients who received first-line EGFR-TKIs and evaluated the PD-L1 tumor proportion score (TPS) using the 22C3 pharmDx assay. We investigated the distribution of patients with different PD-L1 TPS values, followed by analysis of response rate (RR), survival rate, and incidence of secondary T790M mutation according to the PD-L1 TPS group.
Results
Among the 131 patients analyzed, the proportion of patients with PD-L1 TPS ≥ 50%, 1%-49%, and < 1%, was 17.6%, 32.8%, and 49.6%, respectively. The RR was significantly lower in the group with PD-L1 TPS ≥ 50% than in the other groups (43.5% vs. 72.1% vs. 78.5%, all p = 0.001). In multivariate analysis, PD-L1 TPS ≥ 50% was independently associated with a significantly shorter PFS in the overall population (hazard ratio [HR] = 2.64, p = 0.004), and associated with shorter OS in patients with exon 19 deletion (HR = 2.55, p = 0.041) compared with PD-L1 TPS < 50%. In addition, the frequency of secondary T790M mutation after TKI failure was significantly lower in the group with PD-L1 TPS ≥ 50% than in the other groups (13.3% vs. 40.0% vs. 53.3%, all p = 0.001). PD-L1 TPS ≥ 50% was an independent predictor of a lower frequency of this mutation (HR = 0.63, p = 0.043).
Conclusion
High PD-L1 expression was associated with unfavorable clinical outcome, and less development of secondary T790M mutation, suggesting a distinct subgroup warranting active surveillance and tailored therapeutic approach.
