| First Author | Sun Y | Year | 2021 |
| Journal | Sci Adv | Volume | 7 |
| Issue | 38 | Pages | eabc8145 |
| PubMed ID | 34524841 | Mgi Jnum | J:324566 |
| Mgi Id | MGI:6788015 | Doi | 10.1126/sciadv.abc8145 |
| Citation | Sun Y, et al. (2021) NSG-Pro mouse model for uncovering resistance mechanisms and unique vulnerabilities in human luminal breast cancers. Sci Adv 7(38):eabc8145 |
| abstractText | Most breast cancer deaths are caused by estrogen receptor-alpha-positive (ER(+)) disease. Preclinical progress is hampered by a shortage of therapy-naive 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-IL2Rgamma (NSG) mouse (NSG-Pro) with physiological hPRL levels. Here, we show that NSG-Pro mice facilitate establishment of therapy-naive, 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 breast cancer metastases and document divergent biology and drug responsiveness of tumors grown in NSG-Pro versus NSG mice. Oncogenomic analyses of PDX lines in NSG-Pro mice revealed clinically relevant therapy-resistance mechanisms and unexpected, potently actionable vulnerabilities such as DNA-repair aberrations. The NSG-Pro mouse unlocks previously inaccessible precision medicine approaches for ER(+) breast cancers. |
