NSG-Pro mouse model for uncovering resistance mechanisms and unique vulnerabilities in human luminal breast cancers.

ABSTRACT: Most breast cancer deaths are caused by estrogen receptor-α–positive (ER⁺) disease. Preclinical progress is hampered by a shortage of therapy-naïve ER⁺ tumor models that recapitulate metastatic progression and clinically relevant therapy resistance. Human prolactin (hPRL) is a risk factor for primary and metastatic ER⁺ breast cancer. Because mouse prolactin fails to activate hPRL receptors, we developed a prolactin-humanized Nod-SCID-IL2Rγ (NSG) mouse (NSG-Pro) with physiological hPRL levels. Here, we show that NSG-Pro mice facilitate establishment of therapy-naïve, estrogen-dependent PDX tumors that progress to lethal metastatic disease. Preclinical trials provide first-in-mouse efficacy of pharmacological hPRL suppression on residual ER⁺ human

SUBMITTER: Sun Y 

PROVIDER: S-EPMC8443188 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature