2023 World Conference on Lung Cancer (Posters)-P1.06. Trametinib Plus ANTI-PD-1 Immunotherapy Impairs Tumor Growth and Increases Survival of Lung Cancer through ID1 Downregulation

P1.06. Trametinib Plus ANTI-PD-1 Immunotherapy Impairs Tumor Growth and Increases Survival of Lung Cancer through ID1 Downregulation - PDF(Slides)

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Researchers from various institutions in Spain have conducted a study to evaluate the effects of the MEK1/2 inhibitor trametinib on lung cancer cells. The study focused on the role of the inhibitor of differentiation-1 gene (Id1), as it is involved in various cellular processes, including tumor growth and immune response. <br /><br />The researchers found that trametinib reduced Id1 expression in KRAS-mutant lung adenocarcinoma (LUAD) cells both in vitro and in vivo. This reduction was achieved through downregulation of the Id1 protein via proteasome activation. Trametinib also impaired tumor growth in LUAD cells.<br /><br />Additionally, the study showed that trametinib sensitized KRAS-mutant LUAD tumors to anti-PD-1 immunotherapy through Id1 downregulation. The combination of trametinib and anti-PD-1 monoclonal antibodies (mAbs) enhanced PD-L1 expression and increased the infiltration of anti-tumor CD8 T cells, resulting in reduced tumor growth and improved overall survival in mouse models.<br /><br />The study suggests that trametinib could be a potential therapeutic strategy for downregulating Id1 levels in KRAS-mutant LUAD tumors. It also highlights the role of Id1 as a target to restore sensitivity to MEK inhibitors. Additionally, the findings demonstrate the potential of trametinib to sensitize KRAS-driven lung tumors to anti-PD-1/PD-L1 blockade therapies.<br /><br />Overall, this study provides preclinical evidence for the efficacy of trametinib in combination with anti-PD-1 immunotherapy for the treatment of lung cancer. The findings suggest that targeting Id1 and utilizing trametinib as a therapeutic agent could be a promising approach for managing the disease.

Asset Subtitle

Ignacio Gil-Bazo

Meta Tag

Speaker Ignacio Gil-Bazo

Topic Tumor Biology: Preclinical Biology - Tumor Immunity

Keywords

MEK1/2 inhibitor

trametinib

lung cancer cells

Id1 gene

tumor growth

immune response

KRAS-mutant lung adenocarcinoma

proteasome activation

anti-PD-1 immunotherapy

PD-L1 expression