2022 World Conference on Lung Cancer (ePosters)-EP08.02-022. Investigating Partners in Crime: Osimertinib Resistance Mechanisms in Non-small Cell Lung Cancer Using Focused CRISPR Screen

EP08.02-022. Investigating Partners in Crime: Osimertinib Resistance Mechanisms in Non-small Cell Lung Cancer Using Focused CRISPR Screen

Back to course

Pdf Summary

The document discusses a study conducted to investigate mechanisms of resistance to the drug osimertinib in non-small cell lung cancer (NSCLC). NSCLC is the most common form of lung cancer, accounting for 85% of cases. EGFR mutations, which can be targeted by tyrosine kinase inhibitors (TKIs), have been identified as a driving mechanism in NSCLC adenocarcinomas. Osimertinib is a third-generation TKI that has recently been approved for use in the first-line treatment of advanced NSCLC. However, resistance to TKIs, including osimertinib, is a common problem in the treatment of NSCLC.<br /><br />The study aimed to identify potential druggable interactions with the EGFR pathway that could be targeted to overcome acquired resistance to osimertinib. The researchers focused on transcriptional and epigenetic mechanisms that may drive resistance. They developed a gRNA library enriched for epigenetic and transcriptional factors and used high-throughput methodologies such as RNA-seq analysis and a focused CRISPR/Cas9 screen to identify genes involved in resistance.<br /><br />The document mentions the development of a HCC827-OsiR subline, preparation of a gRNA library for the CRISPR screen, RNA-seq analysis for synthetic lethal interactions, and characterization of the HCC827-OsiR subline. It also highlights the candidates identified as potentially involved in osimertinib resistance through the CRISPR screen and RNA-seq analysis.<br /><br />Overall, the study aims to deepen understanding of osimertinib resistance in NSCLC and identify potential targets for future therapies to overcome this resistance. The findings of this study could have implications for improving the treatment outcomes of patients with NSCLC.

Asset Subtitle

Bengisu Uluata Dayanc

Meta Tag

Speaker Bengisu Uluata Dayanc

Topic Metastatic Non-small Cell Lung Cancer - Molecular Targeted Treatments

Keywords

drug resistance

osimertinib

NSCLC

EGFR mutations

tyrosine kinase inhibitors

transcriptional mechanisms

epigenetic mechanisms

CRISPR/Cas9 screen

RNA-seq analysis

therapy targets