Tyrosine phosphoproteome profiling identifies cell-intrinsic signals limiting the efficacy of tyrosine kinase inhibitor therapies - PubMed
4 hours ago
- #Tyrosine Kinase Inhibitors
- #Drug Resistance
- #Phosphoproteomics
- Tyrosine phosphoproteome profiling identified cell-intrinsic signals that limit tyrosine kinase inhibitor (TKI) efficacy in cancer.
- TKI-tolerant cell lines showed a dampened phosphotyrosine response to treatment compared to sensitive lines, despite similar driver TK inhibition.
- All tolerant lines exhibited hyperactivity of SRC family kinases (SFKs) or ABL1/2 kinases, even without genetic mutations in these pathways.
- SFK/ABL inhibitors demonstrated potent synergy with TKIs in combination experiments, suggesting a therapeutic strategy to overcome TKI resistance.