Study 1: Anti-HER2 therapies treating abnormal HER2 signaling in HER2-negative xenograft tumor models
- Previous clinical trials have indicated that there is a weak correlation between HER2 expression levels and HER2 targeted therapy benefit. To evaluate whether HER2-negative tumors with abnormal HER2 signaling may respond to anti-HER2 drugs, H2073 and BT483 cell lines were studied in mouse xenograft models.
- H2073, a non-small cell lung cancer cell line, and BT483, a breast cancer cell line, were each found by the CELsignia test to have abnormal HER2 signaling despite having normally expressed, non-amplified HER2.
- In the H2073 xenograft model, mice were dosed daily for 19 days with afatinib, an irreversible EGFR, HER2, HER4 tyrosine kinase inhibitor. In the BT483 xenograft model, mice were dosed daily for 20 days with lapatinib, a reversible EGFR and HER2 tyrosine kinase inhibitor.
- Tumor growth was significantly inhibited by afatinib (95%) and lapatinib (50%) in their respective xenograft models, demonstrating that abnormal HER2-driven signaling in HER2-negative cancers is oncogenic and responsive to treatment with anti-HER2 drugs.
Tumor Growth Inhibition using HER2 inhibitors in HER2-negative xenograft models