2024-SABCS-Meeting-Preview - 5

IN ER+/HER2- METASTATIC BREAST CANCER (mBC)
A NEW WAVE OF ER DEGRADATION
IS TAKING SHAPE
Research is exploring novel mechanisms that target estrogen receptors (ERs), including
PROTAC ER degraders, which are designed to directly induce ER degradation.1-5
ER activity frequently persists
over the course of ER+ disease.
ER+ breast cancer is often dependent
on the ER pathway for proliferation,
survival, and progression.2,6-8
PROTAC ER degraders are
designed to harness the natural
cellular process of the ubiquitinproteasome
system to directly
induce ER degradation.1,6
Ongoing studies are investigating novel ER-targeting approaches,
which may lead to new options for patients with ER+/HER2- mBC.2-4,6,7,9-11
Scan the QR code or visit ProtacERdegraders.com.
ER = estrogen receptor; ER+ = estrogen receptor-positive; HER2- = human epidermal growth factor receptor 2-negative.
References: 1. 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 2. 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 3. 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 4. Liu Z, Hu M, Yang Y,
et al. An overview of PROTACs: a promising drug discovery paradigm. Mol Biomed. 2022;3:46. doi:10.1186/s43556-022-00112-0 5. 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 6. 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 7. Nardone A, De Angelis C, Trivedi MV, Osborne CK, Schiff R. The changing role of ER in
endocrine resistance. Breast. 2015;24(suppl 2):S60-S66. doi:10.1016/j.breast.2015.07.015 8. Osborne CK, Schiff R. Mechanisms of endocrine resistance
in breast cancer. Annu Rev Med. 2011;62:233-247. doi:10.1146/annurev-med-070909-182917 9. Burke MR, Smith AR, Zheng G. Overcoming cancer drug
resistance utilizing PROTAC technology. Front Cell Dev Biol. 2022;10:872729. doi:10.3389/fcell.2022.872729 10. Stravodimou A, Voutsadakis IA. The
future of ER+/HER2− metastatic breast cancer therapy: beyond PI3K inhibitors. Anticancer Res. 2020;40:4829-4841. doi:10.21873/anticanres.14486
11. Lu Y, Liu W. Selective estrogen receptor degraders (SERDs): a promising strategy for estrogen receptor positive endocrine-resistant breast cancer.
J Med Chem. 2020;63:15094-15114. doi:10.1021/acs.jmedchem.0c00913
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2024-SABCS-Meeting-Preview

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