Table 2.
Correlation of ER-472 antitumor activity to NRP1 expression in tumor lysates in multiple xenograft models. Antitumor activity was assessed for ER-472 administered i.v. on a Q4Dx3 schedule, at ¼ to full MTD doses in multiple xenograft models. NRP1 expression in tumors was assessed by mRNA analysis and/or protein detection by western blot or IHC. Reasonable correlation was determined for 11 of the 13 models
| Xenograft Model | Antitumor Activity | Human NRP1 Expression | Correlation of efficacy to NRP1 | ||
|---|---|---|---|---|---|
| MTD | ½ MTD | ¼ MTD | |||
| MIA PaCa-2 | ++++ | – | nd | low | yes |
| BxPC3 | ++ | – | nd | low | yes |
| PC-3 | ++++ | ++++ | ++ | high | yes |
| SK-N-MC | – | nd | nd | low | yes |
| TC-71 | – | nd | nd | low | yes |
| MDA-MB-231 | ++++ | + | + | high | yes |
| HT-1080 | +++ | ++ | – | high | yes |
| U-87 MG | +++ | ++ | +/− | high | yes |
| COLO 320DM | +/− | – | nd | low | yes |
| Hs 695 T | ++++ | +++ | + | lowa | no |
| CFPAC-1 | + | – | – | lowb | yesb |
| LOX IMVI | ++ | – | – | high | no |
| HCT 116 | nd | – | nd | low | yes |
aNRP1 expressed at high level in cell line was lost in tumors
bhigh NRP1 expression in tumor lysate by western subsequently deemed predominantly stromal by IHC; CFPAC-1 tumor cells had low NRP1 staining, a likely explanation for poor ER-472 therapeutic activity