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. Author manuscript; available in PMC: 2022 Feb 2.
Published in final edited form as: Nat Cancer. 2021 Aug 2;2:978–993. doi: 10.1038/s43018-021-00237-1

Fig. 2. ESK981 inhibits the growth of diverse preclinical models of prostate cancer in vivo.

Fig. 2.

(a) Castration-resistant VCaP tumors (VCaP CRPC) were established subcutaneously in castrated male SCID mice, and treated with vehicle, 30 mg/kg, or 60 mg/kg ESK981. Average tumor volumes were monitored twice per week, n=number of tumors (left). Individual VCaP CRPC tumor weights were measured at study endpoint, n=number of tumors (middle). Percent body weight changes and dosing schedule of VCaP CRPC model, n=number of mice (right). Data were analyzed by two-tailed unpaired t test and presented as mean ± SEM. N and P-value indicated.

(b) Androgen receptor (AR)+ and ERG+ prostate patient-derived xenograft (PDX) MDA-PCa-146-12 were established subcutaneously in non-castrated SCID mice and treated with vehicle or 30 mg/kg ESK981. Average tumor volumes were monitored twice per week, n=number of tumors (left). Tumor weights from individual tumors at study endpoint, n=number of tumors (middle). Percent body weight changes of MDA-PCa-146-12 tumor-bearing mice, n=number of mice (right). Data were analyzed by two-tailed unpaired t test and presented as mean ± SEM. N and P-value indicated.

(c) DU145 tumors were established subcutaneously in non-castrated SCID mice and treated with vehicle or 30 mg/kg ESK981. Average tumor volumes were monitored twice per week, n=number of tumors (left). Individual tumor weights were measured at study endpoint, n=number of tumors (middle). Percent body weight changes of DU145 tumor-bearing mice, n=number of mice (right). Data were analyzed by two-tailed unpaired t test and presented as mean ± SEM. N and P-value indicated.

(d) Neuroendocrine (NEPC) prostate PDX MDA-PCa-146-10 were established in non-castrated SCID mice and treated with vehicle or 30 mg/kg ESK981. Tumor volumes were monitored twice per week, n=number of tumors (left). Individual tumor weights were measured at study endpoint, n=number of tumors (middle). Percent body weight changes of MDA-PCa-146-10 tumor-bearing mice, n=number of mice (right). Data were analyzed by two-tailed unpaired t test and presented as mean ± SEM. N and P-value indicated.

(e) Representative H&E images from three independent experiments showing a dose-dependent induction of a vacuolization morphology from VCaP CRPC tumors treated with vehicle, 30 mg/kg, or 60 mg/kg ESK981 for five days.