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. 2022 Jun 23;82(16):2928–2939. doi: 10.1158/0008-5472.CAN-21-3106

Figure 3.

Figure 3. ER+ ILC L755S is resistant to neratinib but sensitive to poziotinib. A, Dose-response curves for HER2 WT and HER2 L755S cells grown in E2-deprived media, to which increasing concentrations of neratinib and poziotinib were added twice a week for 4 weeks. B, MM134 L755S cells were engrafted into mouse mammary ducts in the absence of E2 until tumor size reached 4.5 × 108 radiance. Bioluminescence images on day 81 (pre-randomization). C, Subsequently, the mice were randomized in the presence of vehicle or fulvestrant (250 mg/kg body weight of mice) or neratinib chow (40 mg/kg) or poziotinib chow (10 mg/kg). Tumor volume was measured by calipers, and tumor growth was monitored. The data are plotted as mean tumor volume in mm3 ± SEM, n = 7–8. The significance (P value) was calculated on day 56 post drug treatment or day 137 post injection, vehicle vs. poziotinib <0.0001, vehicle vs. poziotinib + fulvestrant <0.0001, neratinib vs. poziotinib <0.0001, neratinib vs. poziotinib + fulvestrant <0.0001, neratinib + fulvestrant vs. poziotinib < 0.0001, vehicle vs. neratinib N.S, and vehicle vs. neratinib + fulvestrant N.S. (N.S., no significance). D, Bioluminescence images on day 137 (endpoint). E, Representative bioluminescence ex vivo images of lung and ovaries of L755S mice in the presence or absence of indicated drugs. F, Bioluminescence radiance quantification of lungs and ovaries from E. *, P = 0.01; ***, P = 0.0003.

ER+ ILC L755S is resistant to neratinib but sensitive to poziotinib. A, Dose-response curves for HER2 WT and HER2 L755S cells grown in E2-deprived media, to which increasing concentrations of neratinib and poziotinib were added twice a week for 4 weeks. B, MM134 L755S cells were engrafted into mouse mammary ducts in the absence of E2 until tumor size reached 4.5 × 108 radiance. Bioluminescence images on day 81 (pre-randomization). C, Subsequently, the mice were randomized in the presence of vehicle or fulvestrant (250 mg/kg body weight of mice) or neratinib chow (40 mg/kg) or poziotinib chow (10 mg/kg). Tumor volume was measured by calipers, and tumor growth was monitored. The data are plotted as mean tumor volume in mm3 ± SEM, n = 7–8. The significance (P value) was calculated on day 56 post drug treatment or day 137 post injection, vehicle vs. poziotinib <0.0001, vehicle vs. poziotinib + fulvestrant <0.0001, neratinib vs. poziotinib <0.0001, neratinib vs. poziotinib + fulvestrant <0.0001, neratinib + fulvestrant vs. poziotinib < 0.0001, vehicle vs. neratinib N.S, and vehicle vs. neratinib + fulvestrant N.S. (N.S., no significance). D, Bioluminescence images on day 137 (endpoint). E, Representative bioluminescence ex vivo images of lung and ovaries of L755S mice in the presence or absence of indicated drugs. F, Bioluminescence radiance quantification of lungs and ovaries from E. *, P = 0.01; ***, P = 0.0003.