Study 3: Ovarian xenograft tumor model with abnormal HER2 and c-Met signaling treated with pan-HER and c-Met inhibitors
OVCAR-4, and ovarian cancer cell line, was found by the CELsignia test to have abnormal HER2 and c-Met signaling despite the lack of corresponding EGFR, HER2, HER3 and c-Met mutations
OVCAR-4 was the studied in a xenograft mouse model to evaltuate the anti-tumor effect of treatment with a pan-HER inhibitor and c-Met signaling was oncogenic. Mice were dosed daily with neratinib (pan HER TKI) and tepotinib (c-Met TKI) for 16 days.
The study found that tumor columnes relative to tumor size before treatment were reduced by 40% in the tepotinib + neratinib treated group.
This is the first report of a normally expressed EGFR, HER2, HER3 and c-Met ovarian tumor xenograft model responding to treatment with pan-HER and c-Met inhibitors, demonstrating the oncogenicity of abnormal HER-family and c-Met signaling.