Clinician's guide to targeted estrogen receptor degradation using PROTAC in patients with estrogen receptor-positive metastatic breast cancer.


Journal

Current opinion in oncology
ISSN: 1531-703X
Titre abrégé: Curr Opin Oncol
Pays: United States
ID NLM: 9007265

Informations de publication

Date de publication:
01 11 2023
Historique:
pubmed: 10 7 2023
medline: 10 7 2023
entrez: 10 7 2023
Statut: ppublish

Résumé

Metastatic breast cancer (MBC) remains a major clinical challenge, necessitating the development of innovative therapeutic strategies. Estrogen receptor (ER) degradation using proteolysis-targeting chimeras (PROTAC) has emerged as a promising approach for overcoming acquired resistance to endocrine therapy. This review will summarize recent findings, highlighting the role of ER degradation by PROTAC in patients with MBC. The application of PROTAC technology for ER degradation has demonstrated initial success in preclinical and early clinical studies. PROTACs, consisting of an ER-targeting moiety, an E3 ubiquitin ligase-recruiting moiety, and a linker, facilitate ER ubiquitination and subsequent proteasomal degradation. Yet, significant challenges persist in the clinical translation of ER degradation by PROTAC. These include the optimization of PROTAC design, elucidation of mechanisms underlying resistance to PROTAC-induced ER degradation, and identification of predictive biomarkers for patient stratification. Additionally, addressing potential off-target effects and toxicity profiles remains a critical aspect of developing PROTAC-based therapies. Recent data demonstrate the potential of ER degradation by PROTAC as a therapeutic strategy for patients with MBC. Continued research efforts and development of synergistic combinations are crucial for further advancing PROTAC-based therapies and improving outcomes in patients with MBC.

Identifiants

pubmed: 37427531
doi: 10.1097/CCO.0000000000000972
pii: 00001622-202311000-00004
pmc: PMC10566586
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

472-478

Informations de copyright

Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.

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Auteurs

Albert Grinshpun (A)

Medical Oncology, Dana-Farber Cancer Institute.
Breast Oncology Program, Dana-Farber Brigham Cancer Center.
Harvard Medical School, Boston, MA, USA.

Classifications MeSH