2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.12F.01 Genome-wide CRISPR-Cas9 Screening Identifies ITGA8 Responsible for Abivertinib Sensitivity in Lung Adenocarcinoma

EP.12F.01 Genome-wide CRISPR-Cas9 Screening Identifies ITGA8 Responsible for Abivertinib Sensitivity in Lung Adenocarcinoma

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The study conducted by Xuanguang Li from Tianjin Medical University aimed to address the challenge of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in lung adenocarcinoma. Using a genome-wide CRISPR-Cas9 screening approach, the research identified ITGA8 as a key gene influencing the sensitivity of lung adenocarcinoma cells to abivertinib, an EGFR-TKI.<br /><br />The study first utilized a CRISPR-Cas9 whole-genome library to pinpoint genes that could enhance cancer cell sensitivity to abivertinib. Techniques like RT-qPCR, western blot analysis, and various cell assays were employed to understand ITGA8's role in influencing the sensitivity and biologic behaviors such as proliferation, migration, and invasion of lung adenocarcinoma cells.<br /><br />Results showed that higher ITGA8 expression increased sensitivity to abivertinib, while its knockdown decreased sensitivity. ITGA8 expression was found to be downregulated in lung adenocarcinoma tissues compared to adjacent normal tissues. Enhancing ITGA8 expression was associated with reduced tumor cell proliferation and migration, as well as increased sensitivity to the drug, by modulating the EGFR/FAK/SRC/AKT/MAPK signaling pathway.<br /><br />In vivo experiments confirmed that ITGA8 upregulation notably suppressed tumor growth and increased the efficacy of abivertinib. These findings suggest that ITGA8 is a promising therapeutic target that can enhance treatment effectiveness and delay the development of resistance to EGFR-TKIs in lung adenocarcinoma. Consequently, targeting ITGA8 could offer a novel approach to overcoming drug resistance and improving outcomes for patients with lung adenocarcinoma.

Asset Subtitle

Xuanguang Li

Meta Tag

Speaker Xuanguang Li

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

lung adenocarcinoma

EGFR-TKIs

CRISPR-Cas9

ITGA8

abivertinib

drug resistance

tumor growth

genome-wide screening

signaling pathway

therapeutic target