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The race to develop oral SERDs and other novel estrogen receptor inhibitors: recent clinical trial results and impact on treatment options

Hormonal therapy plays a vital part in the treatment of estrogen receptor–positive (ER +) breast cancer. ER can be activated in a ligand-dependent and independent manner. Currently available ER-targeting agents include selective estrogen receptor modulators (SERMs), selective estrogen receptor degra...

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Autores principales: Wang, Yating, Tang, Shou-Ching
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9560885/
https://www.ncbi.nlm.nih.gov/pubmed/36229710
http://dx.doi.org/10.1007/s10555-022-10066-y
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author Wang, Yating
Tang, Shou-Ching
author_facet Wang, Yating
Tang, Shou-Ching
author_sort Wang, Yating
collection PubMed
description Hormonal therapy plays a vital part in the treatment of estrogen receptor–positive (ER +) breast cancer. ER can be activated in a ligand-dependent and independent manner. Currently available ER-targeting agents include selective estrogen receptor modulators (SERMs), selective estrogen receptor degraders (SERDs), and aromatase inhibitors (AIs). Estrogen receptor mutation (ESR1 mutation) is one of the common mechanisms by which breast cancer becomes resistant to additional therapies from SERMs or AIs. These tumors remain sensitive to SERDs such as fulvestrant. Fulvestrant is limited in clinical utilization by its intramuscular formulation and once-monthly injection in large volumes. Oral SERDs are being rapidly developed to replace fulvestrant with the potential of higher efficacy and lower toxicities. Elacestrant is the first oral SERD that went through a randomized phase III trial showing increased efficacy, especially in tumors bearing ESR1 mutation, and good tolerability. Two other oral SERDs recently failed to achieve the primary endpoints of longer progression-free survival (PFS). They targeted tumors previously treated with several lines of prior therapies untested for ESR1 mutation. Initial clinical trial data demonstrated that tumors without the ESR1 mutation are less likely to benefit from the SERDs and may still respond to SERMs or AIs, including tumors previously exposed to hormonal therapy. Testing for ESR1 mutation in ongoing clinical trials and in hormonal therapy for breast cancer is highly recommended. Novel protein degradation technologies such as proteolysis-targeting chimera (PROTACS), molecular glue degrader (MGD), and lysosome-targeting chimeras (LYTACS) may result in more efficient ER degradation, while ribonuclease-targeting chimeras (RIBOTAC) and small interfering RNA (siRNA) may inhibit the production of ER protein.
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spelling pubmed-95608852022-10-14 The race to develop oral SERDs and other novel estrogen receptor inhibitors: recent clinical trial results and impact on treatment options Wang, Yating Tang, Shou-Ching Cancer Metastasis Rev Clinical Hormonal therapy plays a vital part in the treatment of estrogen receptor–positive (ER +) breast cancer. ER can be activated in a ligand-dependent and independent manner. Currently available ER-targeting agents include selective estrogen receptor modulators (SERMs), selective estrogen receptor degraders (SERDs), and aromatase inhibitors (AIs). Estrogen receptor mutation (ESR1 mutation) is one of the common mechanisms by which breast cancer becomes resistant to additional therapies from SERMs or AIs. These tumors remain sensitive to SERDs such as fulvestrant. Fulvestrant is limited in clinical utilization by its intramuscular formulation and once-monthly injection in large volumes. Oral SERDs are being rapidly developed to replace fulvestrant with the potential of higher efficacy and lower toxicities. Elacestrant is the first oral SERD that went through a randomized phase III trial showing increased efficacy, especially in tumors bearing ESR1 mutation, and good tolerability. Two other oral SERDs recently failed to achieve the primary endpoints of longer progression-free survival (PFS). They targeted tumors previously treated with several lines of prior therapies untested for ESR1 mutation. Initial clinical trial data demonstrated that tumors without the ESR1 mutation are less likely to benefit from the SERDs and may still respond to SERMs or AIs, including tumors previously exposed to hormonal therapy. Testing for ESR1 mutation in ongoing clinical trials and in hormonal therapy for breast cancer is highly recommended. Novel protein degradation technologies such as proteolysis-targeting chimera (PROTACS), molecular glue degrader (MGD), and lysosome-targeting chimeras (LYTACS) may result in more efficient ER degradation, while ribonuclease-targeting chimeras (RIBOTAC) and small interfering RNA (siRNA) may inhibit the production of ER protein. Springer US 2022-10-14 2022 /pmc/articles/PMC9560885/ /pubmed/36229710 http://dx.doi.org/10.1007/s10555-022-10066-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Clinical
Wang, Yating
Tang, Shou-Ching
The race to develop oral SERDs and other novel estrogen receptor inhibitors: recent clinical trial results and impact on treatment options
title The race to develop oral SERDs and other novel estrogen receptor inhibitors: recent clinical trial results and impact on treatment options
title_full The race to develop oral SERDs and other novel estrogen receptor inhibitors: recent clinical trial results and impact on treatment options
title_fullStr The race to develop oral SERDs and other novel estrogen receptor inhibitors: recent clinical trial results and impact on treatment options
title_full_unstemmed The race to develop oral SERDs and other novel estrogen receptor inhibitors: recent clinical trial results and impact on treatment options
title_short The race to develop oral SERDs and other novel estrogen receptor inhibitors: recent clinical trial results and impact on treatment options
title_sort race to develop oral serds and other novel estrogen receptor inhibitors: recent clinical trial results and impact on treatment options
topic Clinical
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9560885/
https://www.ncbi.nlm.nih.gov/pubmed/36229710
http://dx.doi.org/10.1007/s10555-022-10066-y
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