tamoxifen

We previously showed that PR mediates expansion of cancer stem-like cell (CSC) populations and promotes tamoxifen resistance in nuclear ER/PR transcriptional complexes...The UPR activator ErSO, but not UPR inhibitors, blocked expansion of CSCs in WT as well as Y537S ER + models. Together, our findings demonstrate a critical interplay between PR and mutant ER function and provide insight into PR-driven pathways including hyperactivation of the stress-sensing UPR that can be exploited as potential therapeutic avenues in advanced ER+ breast cancer.

Finally, we identified a resistance and stemness marker signature induced by CPF+TAM that closely resembles the profile observed in the dataset of patients who acquired TAM resistance. Our findings show that CPF promotes an undifferentiated basal-like cell phenotype that contributes to TAM resistance, reinforcing the need for global restrictions to safeguard public health.

Inhibition of the RAD51B-EZH2 axis allows the re-expression of functional ERα, making TNBC targetable by endocrine therapy. Consistently, the combination of EZH2 inhibitor with tamoxifen effectively reduces TNBC progression, suggesting that the RAD51B-EZH2 axis is a potential therapeutic target for TNBC.

Our study identified that NSUN7 regulates key oncogenic pathways associated with tamoxifen resistance and metastasis. Its suppression enhanced tamoxifen sensitivity and reduced metastatic potential, collectively highlighting NSUN7 as a novel driver of tamoxifen resistance and a potent therapeutic target in estrogen receptor-positive breast cancer.

In both pre- and postmenopausal women, there is no difference in 10-year OS or LR between anastrozole and tamoxifen for BC patients with low Oncotype RS. We conclude that Stage 1-3, T1-T3 pre- and postmenopausal BC patients with Oncotype RS between 0 and 17 can safely choose either medication. This finding is of particular importance for premenopausal women who wish to avoid the adverse side effects of medically induced menopause and bone deterioration associated with the anastrozole and ovarian suppression approach.

(Z)-endoxifen (hereafter endoxifen), the most abundant active tamoxifen metabolite, has emerged as a promising drug candidate due to its superior anti-estrogenic activity and favorable side effect profile...Resistant cells were characterized by stronger inhibition of the estrogen response, partial retention of endoxifen's antiproliferative effects, acquired activation of proinflammatory pathways and epithelial-mesenchymal transition (EMT), activation of the mTOR pathway (contrasting with its inhibition in sensitive cells), and elevated levels of PKCβ. These resistance-specific changes may potentially drive an endoxifen resistance phenotype and, therefore, proteins involved in these pathways may be proposed as potential therapeutic targets for overcoming endoxifen resistance in breast cancer.

Combinatorial effects with hormone therapies (tamoxifen, fulvestrant, and letrozole) and the AKT inhibitor MK2206 were evaluated. Xanthene- and pyran-based hybrids-particularly SJ028, SJ064, and SJ078-showed strong antitumor activity through apoptosis induction, cell cycle arrest, and PI3K/AKT pathway modulation. Their preserved efficacy in resistant models and synergistic interactions with hormone therapies contrasted with the antagonism observed with AKT inhibition, highlighting their potential as promising candidates for the treatment of hormone-responsive and -resistant cancers.

Anti-inflammatory and respiratory drugs, including glucocorticoids, phosphodiesterase-4 (PDE4) inhibitors, macrolide antibiotics, montelukast, and nonsteroidal anti-inflammatory drugs (NSAIDs), suppress MMP-9-driven airway inflammation and pathological tissue remodeling in asthma, COPD, and acute lung injury. Tetracycline derivatives, particularly sub-antimicrobial dose doxycycline, directly inhibit MMP-9 activity and are clinically validated in the treatment of periodontal disease and vascular remodeling. Hormone-related therapies such as rapamycin, estradiol, and tamoxifen exert tissue- and disease-specific effects on MMP-9 within endocrine and oncologic pathways...Taken together, these findings position MMP-9 as a modifiable and clinically relevant therapeutic target. The systematic integration of approved pharmacologic agents with lifestyle and nutritional interventions into disease-specific treatment paradigms may facilitate safer, context-specific modulation of MMP-9 activity and unveil novel opportunities for therapeutic repurposing.

Collectively, our findings identified STAMBP as a prognostic marker and demonstrated its dual role in driving ER-positive BRCA malignancy and mediating endocrine resistance. Targeting STAMBP may represent an innovative approach to improve endocrine therapeutic efficacy in ER-positive BRCA.

Toremifene exhibits potent chemopreventive activity by targeting MTHFD1L-mediated metabolic dysregulation and ROS-driven apoptosis, offering a promising alternative to tamoxifen for breast cancer prevention.

Mice received tamoxifen at six weeks and were evaluated with or without a 5-day administration of 1.5% dextran sulfate sodium (DSS)...Although DSS did not alter immune infiltration in proximal tumors, regulatory T cells and M2 macrophages were elevated in APC; KRAS compared to APC mutants, suggesting immunosuppressive TME. These findings indicate that transient inflammation promotes CRC development in APC mutant mice.

Subset of AI mice had long-term sustained release tamoxifen placed subscapular on day 8 postpartum...Early metabolic phenotypes in AI and GI glands may be caused by differences in adipocyte repopulation related to estrogen signaling. Long-term metabolic effects of AI lead to similar metabolic effects found in breast cancer.