arzoxifene (LY353381) / Eli Lilly - LARVOL DELTA

Estrogen Promotes Endometrial Cancer Development by Modulating ZNF626, SLK, and RFWD3 Gene Expression and Inducing Immune Inflammatory Changes. (PubMed, Biomedicines) - "Ishikawa cells and ECC-1 cells were stimulated with estradiol (E2) or the selective estrogen receptor modulator Arzoxifene, and qPCR was performed to measure gene expression changes... Estrogen promotes cell proliferation and inhibits apoptosis by upregulating ZNF626 and SLK, while downregulating RFWD3. Furthermore, estrogen induces a shift in the tumor microenvironment, characterized by a reduction in memory CD4+ T cells and a transition from M1 to M2 macrophage phenotypes, thus facilitating the onset and progression of EC."

Journal • Endometrial Cancer • Oncology • Solid Tumor • CD4 • RFWD3

Risk-reducing medications and primary breast cancer prevention: a network meta-analysis of randomized controlled trials. (SABCS 2024) - "These medications included tamoxifen, raloxifene, third-generation SERMs (arzoxifene, bazedoxifene, lasofoxifene), AIs (anastrozole, exemestane), statins (pravastatin, simvastatin, lovastatin), thiazolidinediones (rosiglitazone, pioglitazone), sulfonylurea, metformin, metformin plus sulfonylurea, fenretinide, tamoxifen plus fenretinide, calcium, and calcium plus vitamin D. For the secondary analysis, 16 studies evaluating AIs, tamoxifen, and raloxifene were included for invasive breast cancer...Conclusions These results offer a comprehensive comparative analysis of risk-reducing medications in relation to breast cancer. Findings can guide future research in breast cancer prevention as well as clinical considerations and guidelines on breast cancer chemoprevention."

Retrospective data • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor

Novel Advances in the Role of Selective Estrogen Receptor Modulators in Hormonal Replacement Therapy: A Paradigm Shift. (PubMed, Cureus) - "First-generation SERMs, such as Tamoxifen, are used in the management protocol for breast cancer, which is estrogen receptor (ER-positive). Raloxifene is a second-generation SERM that is a valuable adjunct used to treat and prevent osteoporosis in postmenopausal women and prevent compression fractures of the vertebral column...This article delves into the world of SERMs, including their development and discovery. The newer SERMs in late development, ospemifene, lasofoxifene, bazedoxifene, and arzoxifene, are described in detail."

Journal • Review • Breast Cancer • Cardiovascular • CNS Disorders • Developmental Disorders • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Musculoskeletal Diseases • Oncology • Osteoporosis • Rheumatology • Solid Tumor • Uterine Cancer

Presurgical Window Studies for Drug Development, Studies of Resistance and Patient Management (GBCC 2022) - "We and others have exploited this window for assessing the pharmacolog-ical dose-related activity and for identifying the responsive population of drugs under development for breast cancer (e.g. faslodex, arzoxifene) or drugs whose target population might be extended (eg lapa-tinib). Detailed study of this relationship is needed to ensure that im-mune therapy is not detrimental to clinical outcome of patients with ER+ve disease.Given the emphasis on RNAseq analysis for changes in gene expression due to treatment it is critical that the potential for artefactual changes is recognised. This is best done by the inclusion of a no treat-ment control arm."

Clinical • Breast Cancer • Oncology • Solid Tumor • ER

Novel Selective Estrogen Receptor Downregulators (SERDs) Developed Against Treatment-Resistant Breast Cancer. (PubMed) - J Med Chem - "The clinical SERD, fulvestrant, is hampered by intramuscular administration and undesirable pharmacokinetics. Resistance to the selective estrogen receptor modulator (SERM) tamoxifen and to aromatase inhibitors that lower circulating estradiol occurs in up to 50% of patients, generally leading to an endocrine-independent ER+ phenotype. Novel SERDs were designed using the 6-OH-benzothiophene (BT) scaffold common to arzoxifene and raloxifene. Treatment-resistant (TR) ER+ cell lines (MCF-7:5C and MCF-7:TAM1) were used for optimization, followed by validation in the parent endocrine-dependent cell line (MCF-7:WS8), in 2D and 3D cultures, using ERα in-cell westerns, ERE-luciferase, and cell viability assays, with 2 (GDC-0810/ARN-810) used for comparison. Two BT SERDs with superior in vitro activity to 2 were studied for bioavailability and shown to cause regression of a TR, endocrine-independent ER+ xenograft superior to 2."

Journal • Biosimilar • Breast Cancer • Hormone Receptor Breast Cancer • Oncology

LY353381 in Preventing Breast Cancer in Women With Hyperplasia (clinicaltrials.gov) - P2; N=199; Completed; Sponsor: University of Kansas; Active, not recruiting ➔ Completed

Clinical • Trial completion

Inhibition of Human SULT2A1-Catalyzed Sulfonation of Lithocholic Acid, Glycolithocholic Acid, and Taurolithocholic Acid by Selective Estrogen Receptor Modulators and Various Analogues and Metabolites. (PubMed, J Pharmacol Exp Ther) - "The present study was done to characterize the sulfonation of LCA, GLCA, and TLCA and to investigate whether triphenylethylene (clomifene, tamoxifen, toremifene, ospemifene, droloxifene), benzothiophene (raloxifene, arzoxifene), tetrahydronaphthalene (lasofoxifene, nafoxidine), indole (bazedoxifene), and benzopyran (acolbifene) classes of selective estrogen receptor modulator (SERM) inhibit LCA, GLCA, and TLCA sulfonation. The findings provide an insight into the structural features of specific SERMs that contribute to their inhibition of SULT2A1-catalyzed LCA sulfonation. Inhibition of LCA, GLCA, and TLCA detoxification by a SERM may provide a biochemical basis for adverse effects associated with a SERM."

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