.Antiestrogens in combination with immune checkpoint inhibitors in breast cancer immunotherapy

Publication date: Available online 19 June 2019Source: The Journal of Steroid Biochemistry and Molecular BiologyAuthor(s): Diana C. Márquez-Garbán, Gang Deng, Begonya Comin-Anduix, Alejandro J. Garcia, Yanpeng Xing, Hsiao-Wang Chen, Gardenia Cheung-Lau, Nalo Hamilton, Michael E. Jung, Richard J. PietrasAbstractBreast cancers (BC) with expression of estrogen receptor-alpha (ERα) occur in more than 70% of newly-diagnosed patients in the U.S. Endocrine therapy with antiestrogens or aromatase inhibitors is an important intervention for BCs that express ERα, and it remains one of the most effective targeted treatment strategies. However, a substantial proportion of patients with localized disease, and essentially all patients with metastatic BC, become resistant to current endocrine therapies. ERα is present in most resistant BCs, and in many of these its activity continues to regulate BC growth. Fulvestrant represents one class of ERα antagonists termed selective ER downregulators (SERDs). Treatment with fulvestrant causes ERα down-regulation, an event that helps overcome several resistance mechanisms. Unfortunately, full antitumor efficacy of fulvestrant is limited by its poor bioavailability in clinic. We have designed and tested a new generation of steroid-like SERDs. Using ERα-positive BC cells in vitro, we find that these compounds suppress ERα protein levels with efficacy similar to fulvestrant. Moreover, these new SERDs markedly inhibit ERα-positive BC cell trans...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research