Latest generation estrogen receptor degraders for the treatment of hormone receptor-positive breast cancer.
Expert Opin Investig Drugs
; 31(6): 515-529, 2022 Jun.
Article
en En
| MEDLINE
| ID: mdl-34694932
ABSTRACT
INTRODUCTION:
The selective estrogen receptor degrader (SERD) and full receptor antagonist provides an important therapeutic option for hormone receptor (HR)-positive breast cancer. Endocrine therapies include tamoxifen, a selective estrogen receptor modulator (SERM), that exhibits receptor agonist and antagonist activity, and aromatase inhibitors that block estrogen biosynthesis but which demonstrate acquired resistance. Fulvestrant, the only currently approved SERD, is limited by poor drug-like properties. A key focus for improving disease management has been development of oral SERDs with optimized target occupancy and potency and superior clinical efficacy. AREAS COVERED Using PubMed, clinicaltrials.gov, and congress websites, this review explored the preclinical development and clinical pharmacokinetics from early phase clinical studies (2015 or later) of novel oral SERDs, including giredestrant, amcenestrant, camizestrant, elacestrant, and rintodestrant. EXPERT OPINION Numerous oral SERDs are in clinical development, aiming to form the core endocrine therapy for HR-positive breast cancer. Through property- and structure-based drug design of estrogen receptor-binding, antagonism, degradation, anti-proliferation, and pharmacokinetic properties, these SERDs have distinct profiles which impact clinical dosing, efficacy, and safety. Assuming preliminary safety and activity data are confirmed in phase 3 trials, these promising agents could further improve the management, outcomes, and quality of life in HR-positive breast cancer.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Receptores de Estrógenos
Tipo de estudio:
Systematic_reviews
Límite:
Female
/
Humans
Idioma:
En
Revista:
Expert Opin Investig Drugs
Asunto de la revista:
TERAPIA POR MEDICAMENTOS
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos