General mechanistic differences in degradation and antagonistic activity of existing and investigational treatment approaches1,2
PROTAC ER Degraders
Proteolysis-targeting chimera (PROTAC) ER degraders are an investigational class of drugs designed to directly induce ER degradation by recruiting the ubiquitin-proteasome system (UPS) (the body’s own protein disposal system) to target and eliminate the ER protein.1,3-7
SERDs
CERANs
SERMs
SERCAs
AIs
Watch Dr. Telli discuss the spectrum of existing and investigational ER-targeting approaches for ER+/HER2– mBC.
Dr. Telli is a paid consultant of Arvinas.
Learn About the
Rationale for
Targeting ERs
After Progression
Discover the
Mechanism of
PROTAC ER
Degraders
References: 1. Lloyd MR, Wander SA, Hamilton E, Razavi P, Bardia A. Next-generation selective estrogen receptor degraders and other novel endocrine therapies for management of metastatic hormone receptor-positive breast cancer: current and emerging role. Ther Adv Med Oncol. 2022;14:17588359221113694. doi:10.1177/17588359221113694 2. Hanker AB, Sudhan DR, Arteaga CL. Overcoming endocrine resistance in breast cancer. Cancer Cell. 2020;37:496-513. doi:10.1016/j.ccell.2020.03.009 3. Hernando C, Ortega-Morillo B, Tapia M, et al. Oral selective estrogen receptor degraders (SERDs) as a novel breast cancer therapy: present and future from a clinical perspective. Int J Mol Sci. 2021;22:7812. doi:10.3390/ijms22157812 4. Lin X, Xiang H, Luo G. Targeting estrogen receptor α for degradation with PROTACs: a promising approach to overcome endocrine resistance. Eur J Med Chem. 2020;206:112689. doi:10.1016/j.ejmech.2020.112689 5. Békés M, Langley DR, Crews CM. PROTAC targeted protein degraders: the past is prologue. Nat Rev Drug Discov. 2022;21:181-200. doi:10.1038/s41573-021-00371-6 6. Tecalco-Cruz AC, Ramírez-Jarquín JO, Macías-Silva M, Sosa-Garrocho M, López-Camarillo C. Novel breast cancer treatment by targeting estrogen receptor-alpha stability using proteolysis-targeting chimeras (PROTACs) technology. In: Mayrovitz HN, ed. Breast Cancer. Brisbane (AU): Exon Publications; August 6, 2022. 7. Sun X, Gao H, Yang Y, et al. PROTACs: great opportunities for academia and industry. Sig Transduct Target Ther. 2019;4:64. doi:10.1038/s41392-019-0101-6 8. Patel R, Klein P, Tiersten A, Sparano JA. An emerging generation of endocrine therapies in breast cancer: a clinical perspective. NPJ Breast Cancer. 2023;9:20. doi:10.1038/s41523-023-00523-4 9. Patel HK, Bihani T. Selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs) in cancer treatment. Pharmacol Ther. 2018;186:1-24. doi:10.1016/j.pharmthera.2017.12.012