Study 2: Tumor xenograft study vs. CELsignia signaling analysis using c-Met and ErbB targeted therapies
- The HCC1954 breast cancer cell line was found by the CELsignia Test to have abnormal HER2, HER1, and c-Met pathways. The efficacy of different HER family and c-Met as single agents and in combination was also determined ex vivo.
- HCC1954 was then studied in a mouse xenograft model using these same agents to determine the correlation between the ex vivo and in vivo methods of assessing signaling activity and drug efficacy.
- In the xenograft study, mice were dosed daily for 17 days with either a control, neratinib (pan-HER TKI), tepotinib (c-Met TKI), erlotinib (HER1 TKI), erlotinib and tepotinib, or neratinib and tepotinib.
- Each of the mouse xenograft studies yielded results consistent with the results from the ex vivo signaling and drug efficacy analyses performed using the CELsignia Test. Of particular note was the superior tumor growth inhibition of the pan-HER and c-Met inhibitor combination (71%) compared to the EGFR and c-Met inhibitor combination.
|Drug||Signal Inhibition Measured by CELsignia||Xenograft Tumor Reduction vs. control (t-test)|
|Erlotinib (HER1i)||<5%||5% (p=.870)|
|Tepotinib (c-METi)||<5%||10% (p=.780)|
|Neratinib (pan-HERi)||50%||45% (p=0.003)|
|Erlotinib + Tepotinib||48%||47% (p=0.110)|
|Neratinib + Tepotinib||100%||71% (p=0.0003)|