2023 World Conference on Lung Cancer (Posters)-EP02.01. Synergism of KRAS G12C Inhibitor and mTOR Inhibitor in Lung Adenocarcinoma and Squamous Cell Carcinoma

EP02.01. Synergism of KRAS G12C Inhibitor and mTOR Inhibitor in Lung Adenocarcinoma and Squamous Cell Carcinoma - PDF(Slides)

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Researchers conducted a study to evaluate the combination of a KRAS G12C inhibitor and an mTOR inhibitor in lung adenocarcinoma and squamous cell carcinoma. The KRAS G12C inhibitor, which is used to target a specific nucleotide change known as a smoking-induced variant, has been clinically available. The study aimed to determine the effectiveness of combining this inhibitor with another target inhibitor.<br /><br />The study involved analyzing 877 resected lung adenocarcinoma and 113 squamous cell carcinoma cases to determine the incidence of the KRAS G12C variant using ddPCR. The combination effect of the KRAS inhibitor and mTOR inhibitor was evaluated in different cell lines representing lung adenocarcinoma and squamous cell carcinoma using the Chou-Talalay method.<br /><br />The study found that the frequency of KRAS G12C was similar in both adenocarcinoma and squamous cell carcinoma cases. The researchers observed a synergistic effect between the KRAS G12C inhibitor and mTOR inhibitor in both cell lines through MTS assay and Clonogenic assay. The combination of the inhibitors resulted in suppressed cell growth in a dose-dependent manner. Additionally, the expression of pmTOR (S2448) and KRAS was suppressed in the combination treatment.<br /><br />Based on these findings, the researchers concluded that the combination of KRAS G12C inhibitor (AMG-510, MRTX849, and ARS-1620) and mTOR inhibitor (RAD001) showed synergism in both adenocarcinoma and squamous cell carcinoma cell lines. This combination strategy holds promise for the treatment of these two major types of lung cancer.

Asset Subtitle

Masaoki Ito

Meta Tag

Speaker Masaoki Ito

Topic Tumor Biology: Preclinical Biology - Molecular Therapeutic Targets

Keywords

KRAS G12C inhibitor

mTOR inhibitor

lung adenocarcinoma

squamous cell carcinoma

nucleotide change

smoking-induced variant

ddPCR

Chou-Talalay method

synergistic effect

cell growth suppression