2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.12A.07 Restoring Expression of Tumor Suppressor PTEN by Engineered Circular RNA Enhances Osimertinib Sensitivity in Non-Small Cell Lung Cancer

EP.12A.07 Restoring Expression of Tumor Suppressor PTEN by Engineered Circular RNA Enhances Osimertinib Sensitivity in Non-Small Cell Lung Cancer

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The study conducted by Mantang Qiu at Peking University People's Hospital explores the potential of utilizing engineered circular RNA (circRNA) to restore the function of the tumor suppressor gene PTEN, thereby enhancing osimertinib sensitivity in non-small cell lung cancer (NSCLC). The research focuses on the NeoAna circRNA platform, which facilitates the synthesis of circRNAs free of scar sequences, resulting in diminished immunogenic responses compared to other platforms.<br /><br />Key findings demonstrate that the circRNA named cPTEN_NeoAna can significantly increase NSCLC cells' sensitivity to osimertinib both in vitro and in vivo. Cells transfected with cPTEN_NeoAna displayed increased apoptosis and reduced proliferation. In animal models, the treatment led to the smallest tumor volumes compared to controls. Additionally, cPTEN_NeoAna appeared superior to its counterparts, cPTEN_Ana and m1ψ-PTEN, as cells treated with cPTEN_NeoAna and osimertinib showed the lowest proliferation rates and highest apoptosis rates.<br /><br />Mechanistically, PTEN plays a critical role in suppressing the PI3K-AKT pathway and KRAS expression, while it regulates the expression of AKR1C2 and elevates intracellular reactive oxygen species (ROS) levels, contributing to the antitumor effects observed. The overall conclusion is that the NeoAna platform provides a viable method for synthesizing circRNAs with low immunogenicity, with cPTEN_NeoAna showing promise as a therapeutic enhancement for osimertinib in treating NSCLC.<br /><br />This research received funding from the Beijing Nova Program, and further details or inquiries can be directed to Mantang Qiu via email.

Asset Subtitle

Mantang Qiu

Meta Tag

Speaker Mantang Qiu

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

circular RNA

PTEN

osimertinib sensitivity

NSCLC

NeoAna platform

cPTEN_NeoAna

tumor suppressor

PI3K-AKT pathway

reactive oxygen species

Beijing Nova Program