2022 World Conference on Lung Cancer (ePosters)-EP14.02-002. Cisplatin in Combination with Entinostat exerts Synergistic Antineoplastic Activity in Small Cell Lung Cancer

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Researchers have found that the combination of cisplatin and entinostat shows strong synergistic effects in a subset of small cell lung cancer (SCLC) cell lines. This combination therapy resulted in cell death in double resistant SCLC cell lines, suggesting a potential way to overcome therapeutic resistance. Proteomic analysis showed differential expression patterns between the synergistic and additive groups, including changes in cell cycle and DNA damage repair. Additionally, the intracellular platinum content was elevated upon combination treatment. <br /><br />SCLC is a highly aggressive form of lung cancer with a poor survival rate. Platinum-based chemotherapy is a key component of the standard first-line treatment for SCLC, but almost all patients eventually develop resistance to the treatment. Entinostat, a histone deacetylase inhibitor, has been shown to synergize with cisplatin and has been reported to reverse cisplatin resistance in various human cancers.<br /><br />The researchers determined the IC50 values of the drugs using cell viability assays, and correlation analysis demonstrated a significant relationship between entinostat resistance and cisplatin resistance. The combination therapy of entinostat and cisplatin showed strong synergistic effects in certain SCLC cell lines, while additive effects were observed in others.<br /><br />Proteomic analysis was conducted to investigate the underlying mechanism behind the synergistic effects. The analysis revealed differential expression of proteins involved in cell cycle and DNA damage repair pathways between the synergistic and additive cell lines.<br /><br />Further analysis of the cell cycle following combination treatment showed a shift from G1 to S-phase in the synergistic SCLC cells, indicating a potential mechanism for the increased antineoplastic activity.<br /><br />Additionally, the researchers found that the combination treatment led to increased intracellular platinum content. This suggests that the combination therapy may enhance the accumulation of cisplatin within cancer cells and potentially increase its effectiveness.<br /><br />Overall, this study highlights the strong synergistic effects of combining cisplatin and entinostat in a subset of SCLC cell lines, and provides insights into the underlying mechanisms and potential strategies for overcoming therapeutic resistance in SCLC.

Asset Subtitle

Anna Schwendenwein

Meta Tag

Speaker Anna Schwendenwein

Topic Small Cell Lung Cancer and Neuro-endocrine Tumours - Preclinical/Translational

Keywords

cisplatin

entinostat

synergistic effects

small cell lung cancer

therapeutic resistance

proteomic analysis

cell cycle

DNA damage repair

platinum-based chemotherapy

histone deacetylase inhibitor