P1, N=62, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Oct 2025

Tamoxifen is the drug of choice in ER-positive breast cancer, and several studies have shown better disease-free survival in these patients...In addition, a computational approach involving molecular modeling and simulation of phosphorylated and unphosphorylated forms of PAK1 was used to elucidate the dynamics of nuclear localization. Thus, PAK1 phosphorylation by JAK2 is a prerequisite for its nuclear localization and its tumorigenic effects on endometrial cancer cells.

We generated tamoxifen inducible Dab2 conditional knockout system for our study...In patients, TCGA data analysis of skin cancer melanoma (SKCM) showed a trend where high levels of Dab2 correlated with poor overall survival. The present study shows that Dab2 promotes tumour progression in skin SCC.

Depletion or inhibition of GPX4 increases sensitivity to palbociclib and giredestrant, and their combination, in ER+ breast cancer models, with GPX4 null xenografts being highly sensitive to palbociclib. Lipid peroxidation is promoted by a peroxisome AGPAT3-dependent pathway in ER+ breast cancer models, rather than the classical ACSL4 pathway. Our data demonstrate that CDK4/6 and ER inhibition creates vulnerability to ferroptosis induction, that could be exploited through combination with GPX4 inhibitors, to enhance sensitivity to the current therapies in breast cancer.

P1, N=15, Recruiting, EtiraRx Australia Pty Ltd | Not yet recruiting --> Recruiting

P3, N=1156, Not yet recruiting, Alliance for Clinical Trials in Oncology

P=N/A, N=128, Enrolling by invitation, University of Pennsylvania

These findings suggest that PRODH regulates tamoxifen resistance by regulating ferroptosis in tamoxifen-resistant cells.

DTVM outperformed Tamoxifen at 50 µM in the MCF-7 cell line...The differences in docking scores and interaction profiles highlight the potential efficacy and specificity of these compounds in targeting breast and colon cancer cells. These findings highlight the potential of phosphazene-peptide derivatives as therapeutic agents in cancer treatment.

Mice with (itgb1fl/flSCLcre) and without (itgb1fl/fl) tamoxifen inducible stem cell leukemia cre recombinase (SLCcre) expression at 10 days post cre induction had comparable exercise tolerance and pulmonary and cardiac functions. Using robust in vivo experimental platforms (i.e., intravital microscopy and hyperinsulinemic-euglycemic clamp), we show that itgb1fl/flSCLcre mice compared to itgb1fl/fl littermates have, i) deficits in capillary flow rate, flow heterogeneity, and capillary density; ii) impaired insulin-stimulated glucose uptake despite sufficient transcapillary insulin efflux; and iii) reduced insulin-stimulated glucose uptake due to perfusion-limited glucose delivery. Thus, EC itgb1 is necessary for microcirculatory function and to meet the metabolic challenge of insulin stimulation.

In this comprehensive review, we systematically summarize the critical role and intricate molecular mechanisms by which lncRNAs influence the development of tamoxifen resistance in breast cancer. Furthermore, we propose the potential clinical significance of lncRNAs as innovative therapeutic targets and prognostic biomarkers for breast cancer.

P2, N=30, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

Furthermore, we observed a significant downregulation of full length ERα expression in epigenetically edited MCF-7 cells with consequential alteration in cellular response toward estradiol and tamoxifen treatment due to dCas9-HDAC8-EGFP mediated epigenetic editing of the ESR1 gene. Overall, dCas9-HDAC8-EGFP is a novel circuit that enabled downregulation of crucial genes with cellular outcome in breast cancer cells by preferentially inducing H3K9 deacetylation of specific promoter regions.

We did not observe significant associations between CYP2D6 metabolizer status or endoxifen with PFS. Small sample sizes and barriers to adequate samples in this trial prohibited determination of relationship between these markers and PFS.

Our findings showed a significant alteration between PALB2 gene expression in the TAM-treated breast cancer cell line and the control cell line. The quantitative assessment of mentioned genes as possible markers could be considered a non-invasive method for breast cancer in the processes of prognostic evaluations, screening, and treatment monitoring.

Fertility preservation with controlled ovarian stimulation for patients with breast cancer was not found to impair long-term oncologic outcomes, including in emerging clinically relevant subgroups.

This study aimed to analyze the values of the biomarkers ultrasensitive C-reactive protein (PCR_us) and Homocysteine (HCy) after the use of intravascular laser irradiation of blood (ILIB) in mastectomized patients using hormonal blockers Tamoxifen and Aromatase Inhibitors...However, a significant difference between the groups (p < 0.05) for HCy in the 3rd and 4th months. During ILIB Therapy, there was a reduction in HCy, which may favor the improvement of cardiovascular function in these patients undergoing anticancer therapies.

P3, N=320, Active, not recruiting, Genentech, Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Oct 2024 --> Mar 2026

The normal (NOR) and negative (DMBA) control groups were daily treated with the vehicle, while the positive (Tamox) and test (XAE) groups were administered tamoxifen (3.3 mg/kg) and X. aethiopica extract (75, 150, and 300 mg/kg BW), respectively for 20 weeks...Furthermore, there was an elevation in antioxidants (SOD, CAT, and GSH) and a decrease in pro-inflammatory cytokines (INF-γ, TNF-α, IL-12, and IL-6) observed at all tested doses. Overall, X. aethiopica dry fruit displays anticancer potential through caspase-3-dependent apoptosis pathways, alongside antioxidant and anti-inflammatory activities.

Levonorgestrel-releasing intrauterine system (LNG-IUS) has been explored as preventive strategies, but its impact on breast cancer recurrence especially in Progesterone receptor (PR)-positive patient is not clear. Aromatase Inhibitors (AIs) have shown beneficial results in EH after tamoxifen and their role should be explored in further trials.

The results obtained showed that the uptake of [125I]I-AM into MCF-7 cells was found to be inhibited by AM and tamoxifen, suggesting that its uptake is partially mediated by ERα...These results suggested that AM would be a useful platform for the development of a new radiopharmaceutical targeting ERα. Further studies are, however, required to reduce deiodination of &lsqb;125I]I-AM in vivo.

We only administered tamoxifen postoperatively without other adjuvant therapy because her tumor partially expressed hormonal receptors. No signs indicate a recurrence or metastasis in our over 3 year follow-up. The genetic analysis helps in definitively diagnosing breast mucoepidermoid carcinoma, and the treatment strategy should be considered based on the histologic findings.

This patient had a history of right ER/PR positive HER2 negative stage 1 breast cancer s/p lumpectomy with sentinel lymph node biopsy and radiation plus tamoxifen x6 months in 2017...No right-sided sentinel node was identified. The right breast lesions and the left axillary lymph node metastases are all morphologically similar and showed strong ER expression, the results of which are compatible with spreading to the contralateral axilla.

Furthermore, inflammation and fibrosis in the liver were less severe in diabetic MASH using tamoxifen-induced PDGF receptor β (PDGFRβ)-deficient mice (KO) than in control dMASH using floxed mice (FL) at 12 weeks old...An Ingenuity Pathway Analysis of differentially expressed miRNA between FL and KO identified functional networks associated with hepatotoxicity and cancer. Therefore, PDGFRβ signals play important roles in the progression of steatohepatitis and tumorigenesis in MASH, with the modulation of miRNA expression posited as a potential underlying mechanism.

This meta-analysis of observational studies supports a reduction in CBC risk with endocrine therapy among breast cancer survivors, in concert with evidence synthesized from randomized clinical trials, and highlights differences in endocrine therapy effectiveness by ER-status of CBC.

We observed that the novel CSE inhibitor I194496 can reverse TAM resistance in TAM-resistant breast cancer via targeting the PPARγ/ACSL1/STAT3 signalling pathway. Overall, our data indicate that CSE may serve as a biomarker of TAM resistance and that the CSE inhibitor I194496 is a promising candidate for combating TAM resistance.

P1, N=155, Recruiting, Olema Pharmaceuticals, Inc. | N=90 --> 155 | Trial completion date: Aug 2024 --> Jun 2026 | Trial primary completion date: Aug 2024 --> May 2026

The findings suggest that caffeine administration attenuates tamoxifen-induced fatty liver in rats by ameliorating oxidative stress, inflammation, liver injury, and cell damage. Histopathological evidence further supports the protective role of caffeine. This study highlights the potential of caffeine as a therapeutic intervention to counter tamoxifen-induced hepatic complications, contributing to the optimization of breast cancer treatment strategies.

P=N/A, N=112, Not yet recruiting, Aarhus University Hospital

The MUC1/estrogen receptor axis is eventually essential for cancer stem-like features, specifically in HER2-negative cells, and promotes the capability of cancer cells to form mammospheres and express stem-related genes, also reducing their sensitivity to tamoxifen administration. Altogether our findings describe a novel mechanism by which mast cells could increase the aggressiveness of breast cancer uncovering a molecular mechanism displaying differences based on the specific breast cancer subtype.

The current meta-analysis demonstrated an increase of ApoA-I and a decrease of ApoB and lipoprotein(a) levels after treatment with tamoxifen in women.

Our findings demonstrate that the overexpression of PPARγ is a frequent occurrence during acquisition of Tam resistance in luminal A BC cells, and that PPARγ antagonism represents an alternative therapeutic approach for the personalized treatment of BC showing dysregulation of this nuclear receptor.

In the present study, triphenyl phosphonium cationic group-conjugated fisetin (mito-fisetin) was synthesized, and its anticancer activity was investigated in several cellular models of estrogen receptor (ER)-positive breast cancer in vitro and in vivo in proliferating and tamoxifen-promoted senescent states...Senescent breast cancer cells were found to be more sensitive to mito-fisetin treatment than proliferating ones. We postulate that mitochondrial targeting in the case of fisetin may be considered as a promising anticancer and senotherapeutic strategy to eliminate drug-resistant senescent breast cancer cells.

P2, N=200, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

Treatment typically follows protocols for female breast cancer, including surgery, chemotherapy, and hormone therapy, with tamoxifen being commonly used. Further research is needed to better understand its pathogenesis and to develop more effective, tailored treatments.

P3, N=490, Recruiting, Jina Pharmaceuticals Inc.

P3, N=124, Completed, Jina Pharmaceuticals Inc. | Recruiting --> Completed

Male patients with BC had a relatively higher risk of hospitalization (χ2 = 4.83, p = .03) and a lower risk of deaths (χ2 = 5.32, p = .02). Theses finding may assist healthcare professionals in recognizing the TAM-associated AEs and understanding gender differences, potentially improving safety in clinical applications.

This thermal analysis method was used as a surrogate for chromatography as a rapid, effective in-process check method for impurity quantitation to enable the timely release of the final reworked clinical batch. Post release, the % w/w oligomer value determined by calorimetry was in excellent agreement to that obtained by size exclusion chromatography.

Seven drugs were shortlisted for their time-dependent (10-12 days) cytotoxic effect and further narrowed to three effective drugs (e.g., cisplatin, doxorubicin, and hydroxychloroquine). We identified multiple druggable targets and, using ex-vivo methods narrowed multiple drugs to disease-condition-specific therapeutics. We consider that our investigation successfully interconnected the expression data with the functional disease-specific therapeutic investigation and selected drugs can be used for effective resistant treatment with higher therapeutic response.

New analyses can be carried out with specific fold-change thresholds for gene expression, or with different pair-wise combinations between conditions (treatments and/or mouse models). Together, the data generated herein are a useful tool to study hormonal transcriptional responses in prostate and prostate cancer biology.

P2, N=74, Completed, GOG Foundation | Active, not recruiting --> Completed