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Endoxifen, an Estrogen Receptor Targeted Therapy: From Bench to Bedside.
- Source :
-
Endocrinology [Endocrinology] 2021 Dec 01; Vol. 162 (12). - Publication Year :
- 2021
-
Abstract
- The selective estrogen receptor (ER) modulator, tamoxifen, is the only endocrine agent with approvals for both the prevention and treatment of premenopausal and postmenopausal estrogen-receptor positive breast cancer as well as for the treatment of male breast cancer. Endoxifen, a secondary metabolite resulting from CYP2D6-dependent biotransformation of the primary tamoxifen metabolite, N-desmethyltamoxifen (NDT), is a more potent antiestrogen than either NDT or the parent drug, tamoxifen. However, endoxifen's antitumor effects may be related to additional molecular mechanisms of action, apart from its effects on ER. In phase 1/2 clinical studies, the efficacy of Z-endoxifen, the active isomer of endoxifen, was evaluated in patients with endocrine-refractory metastatic breast cancer as well as in patients with gynecologic, desmoid, and hormone-receptor positive solid tumors, and demonstrated substantial oral bioavailability and promising antitumor activity. Apart from its potent anticancer effects, Z-endoxifen appears to result in similar or even greater bone agonistic effects while resulting in little or no endometrial proliferative effects compared with tamoxifen. In this review, we summarize the preclinical and clinical studies evaluating endoxifen in the context of breast and other solid tumors, the potential benefits of endoxifen in bone, as well as its emerging role as an antimanic agent in bipolar disorder. In total, the summarized body of literature provides compelling arguments for the ongoing development of Z-endoxifen as a novel drug for multiple indications.<br /> (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Subjects :
- Animals
Bone and Bones drug effects
Bone and Bones metabolism
Breast Neoplasms drug therapy
Breast Neoplasms metabolism
Breast Neoplasms pathology
Cell Proliferation drug effects
Estrogen Antagonists pharmacology
Estrogen Antagonists therapeutic use
Female
Humans
Molecular Targeted Therapy methods
Receptors, Estrogen drug effects
Selective Estrogen Receptor Modulators pharmacology
Selective Estrogen Receptor Modulators therapeutic use
Tamoxifen pharmacology
Tamoxifen therapeutic use
Receptors, Estrogen antagonists & inhibitors
Tamoxifen analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7170
- Volume :
- 162
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 34480554
- Full Text :
- https://doi.org/10.1210/endocr/bqab191