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Oral Selective Estrogen Receptor Degraders (SERDs) in Breast Cancer: Advances, Challenges, and Current Status.

ABSTRACT: Several endocrine therapies are currently available for the treatment of estrogen receptor (ER) positive breast cancer, but the clinical benefit of these agents is limited by endocrine therapy drug resistance. A common mechanism of endocrine therapy resistance is ESR1 mutations. The first-generation selective estrogen receptor degrader (SERD) fulvestrant has activity against ESR1 mutant tumors but requires intramuscular injection and has poor bioavailability that precludes optimal drug dosing. This led to the development of second-generation SERDs which are potent and have improved oral bioavailability and pharmacokinetics. Several of these oral SERDs are now in phase III trials in both the early and advanced ER positive breast cancer settings. This review summarizes the background of oral SERD development, the current status and future perspectives.

SUBMITTER: Downton T

PROVIDER: S-EPMC9447452 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Oral Selective Estrogen Receptor Degraders (SERDs) in Breast Cancer: Advances, Challenges, and Current Status.

Downton Teesha T Zhou Fiona F Segara Davendra D Jeselsohn Rinath R Lim Elgene E

Drug design, development and therapy 20220902

Several endocrine therapies are currently available for the treatment of estrogen receptor (ER) positive breast cancer, but the clinical benefit of these agents is limited by endocrine therapy drug resistance. A common mechanism of endocrine therapy resistance is <i>ESR1</i> mutations. The first-generation selective estrogen receptor degrader (SERD) fulvestrant has activity against <i>ESR1</i> mutant tumors but requires intramuscular injection and has poor bioavailability that precludes optimal ...[more]

PMID: 36081610

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