The oncogenic EGFR-SHC1 fusion confers insensitivity to EGFR-TKI via dual activation of N-EGFR kinase domain and C-SHC1 phosphorylation sites in lung cancer - PubMed
6 hours ago
- #EGFR-SHC1 fusion
- #TKI resistance
- #NSCLC
- The EGFR-SHC1 fusion in NSCLC shows intrinsic resistance to EGFR-TKI monotherapy.
- The fusion protein activates both the EGFR kinase domain and SHC1 phosphorylation sites, driving ERK/AKT pathway activation.
- Structural modeling revealed SHC1 phosphorylation enables a kinase-independent bypass mechanism.
- Dual inhibition with afatinib and dasatinib induced tumor regression in a TKI-refractory NSCLC patient.
- The study provides a strategy to overcome TKI resistance in patients with EGFR-SHC1 fusion.