The Histone-Modified Landscape: Core Mechanisms of Osimertinib Resistance in EGFR-Mutant Lung Cancer - PubMed
9 hours ago
- #drug resistance
- #epigenetics
- #lung cancer
- Osimertinib is a key targeted therapy for EGFR-mutant non-small cell lung cancer, but resistance develops over time.
- Resistance mechanisms include genetic changes, tumor microenvironment, and cancer stem cells, but these don't fully explain rapid adaptation.
- Epigenetic changes, particularly histone modifications like acetylation, methylation, and lactylation, play a crucial role in resistance.
- These modifications alter chromatin structure, affect gene expression, impair DNA repair, and promote a drug-tolerant state.
- Histone modification patterns may serve as biomarkers for predicting resistance and identifying new drug targets.
- A proposed strategy combines multimodal epigenetic therapies with liquid biopsies to predict and prevent resistance proactively.
- This approach aims to outmaneuver tumor evolution, overcome resistance, and improve patient survival.