The observed effect was ESR1-dependent and effectively blocked by tamoxifen, revealing a ligand-independent activation mechanism...The presence of PSNPs also mitigated AgNPs-induced reduction of BRCA1 expression. This study highlights how nanomaterial-induced ESR1 activation can lead to enhanced epithelial-mesenchymal transition and cell cycle progression, suggesting potential adverse effects of nanomaterials in ER+ cancer proliferation via protein kinase-mediated ESR1 modulation.

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.

P3, N=1000, Recruiting, Olema Pharmaceuticals, Inc. | Not yet recruiting --> Recruiting

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.

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.

P1, N=60, Active, not recruiting, Olema Pharmaceuticals, Inc. | Trial completion date: Jul 2025 --> Mar 2026 | Trial primary completion date: Jan 2025 --> Mar 2026