ELMO2 is a therapeutic vulnerability in mesenchymal-like and drug-resistant non-small cell lung cancer - PubMed
3 hours ago
- #ELMO2
- #synthetic lethality
- #NSCLC resistance
- ELMO2 is identified as a vulnerability in mesenchymal-like and drug-resistant non-small cell lung cancer.
- Suppression of ELMO2 leads to excessive autophagy and cell death by inhibiting FAK activity, with ELMO3 acting as a compensatory paralog.
- ZEB1 represses ELMO3 in mesenchymal-like cells, making them sensitive to ELMO2 blockade, linking it to EGFR inhibitor resistance.
- A small-molecule inhibitor, C52, targets ELMO2 and effectively kills ELMO3-low and EGFR inhibitor-resistant lung cancer cells.
- The study proposes ELMO2 as a therapeutic target for mesenchymal-like and drug-resistant NSCLC through a synthetic lethal interaction with ELMO3.