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. 2016 Oct 18;8(48):83432–83445. doi: 10.18632/oncotarget.12735

Figure 4. E2-independent MCF7mutER(Y537S) tumor xenografts are resistant to tamoxifen (TAM) but regress when TAM is combined with Dinaciclib, given at a dose and schedule that alone has no effect on tumor growth.

Figure 4

A. In study PTC1797, MCF7mutER(Y537S) implanted nude mice showing tumor growth in the absence of exogenous E2 supplementation were allocated to begin treatment at day 24 with either daily sc 0.5 mg tamoxifen citrate (18 mice, red bar) or vehicle (20 mice). At day 35, mice with comparably sized tumors from each group were also begun with ip treatments receiving either vehicle or Dinaciclib (30 mg/kg) twice weekly over the next 14 days. Inset shows % tumor volume change beyond day 35 for TAM (n = 8), Dinaciclib (n = 6), and TAM + Dinaciclib (n = 7) treated tumors. B. In study PTC1854, MCF7mutER(Y537S) implanted nude mice (without E2 supplementation) showing tumor growth at day 8 were randomized into 6 treatment arms (8 mice/arm) to receive sc daily TAM (n = 18, red bar) or vehicle (n = 18) as in PTC1797, and at day 22 to begin ip treatments with vehicle (n = 8) or 30 mg/kg of either Palbociclib or Dinaciclib as shown (vertical arrows). Inset shows representative IP/IB analysis of combination treated tumors harvested 2 h following final ip treatment, 1st IP/IB for pS294 and 2nd IP/IB for total ERα.