What is the mechanism of resistance to lapatinib?

Lapatinib is an orally administered dual tyrosine kinase inhibitor that inhibits both the epidermal growth factor receptor (HER1) and HER2. Although lapatinib may be employed in treating trastuzumab-resistant HER2-positive advanced gastric cancer cases, the primary issue with tyrosine kinase targeted therapies lies in the fact that many tumours fail to respond to the drug or ultimately develop resistance, typically due to the activation of alternative signalling pathways. In vitro studies indicate that FOXO1 acts as a pivotal link between the HER2 and MET signalling pathways through negative cross-regulation, serving as a key regulatory factor in the development of acquired lapatinib resistance in HER2-positive gastric cancer cells.

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