Acquired resistance to fulvestrant and palbociclib is a new challenge to treatment of estrogen receptor positive (ER+) breast cancer. ER is expressed in most resistance settings; thus, bromodomain and extra-terminal protein inhibitors (BETi) that target BET-amplified ER-mediated transcription have therapeutic potential. Novel pyrrolopyridone BETi leveraged novel interactions with L92/L94 confirmed by a cocrystal structure of with BRD4. Optimization of BETi using growth inhibition in fulvestrant-resistant (MCF-7:CFR) cells was confirmed in endocrine-resistant, palbociclib-resistant, and mutant cell lines. was more potent in MCF-7:CFR cells than six BET inhibitors in clinical trials. Transcriptomic analysis differentiated from the benchmark BETi, JQ-1, showing downregulation of oncogenes and upregulation of tumor suppressors and apoptosis. The therapeutic approach was validated by oral administration of in orthotopic xenografts of endocrine-resistant breast cancer in monotherapy and in combination with fulvestrant. Importantly, at an equivalent dose in rats, thrombocytopenia was mitigated.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258866 | PMC |
| http://dx.doi.org/10.1021/acs.jmedchem.0c00456 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The Role of Race/Ethnicity on the Association between Neighborhood Deprivation and Breast Cancer Outcomes among Kentucky Breast Cancer Patients years 2010-2022.
Cancer Epidemiol Biomarkers Prev
January 2025
University of Kentucky, Lexington, KY, United States.
Background: Kentucky is within the top five leading states for breast mortality nationwide. This study investigates the association between neighborhood socioeconomic disadvantage and breast cancer outcomes, including surgical treatment, radiation therapy, chemotherapy, and survival, and how associations vary by race and ethnicity in Kentucky.
Methods: We conducted a retrospective cohort analysis using data from the Kentucky Cancer Registry (KCR) for breast cancer patients diagnosed between 2010 and 2017, with follow-up through December 31, 2022.
Identifying and targeting key driver genes for collagen production within the 11q13/14 breast cancer amplicon.
Mol Cancer Res
January 2025
Fox Chase Cancer Center, Philadelphia, PA, United States.
Breast cancers of the IntClust-2 type, characterized by amplification of a small portion of chromosome 11, have a median survival of only five years. Several cancer-relevant genes occupy this portion of chromosome 11, and it is thought that overexpression of a combination of driver genes in this region is responsible for the poor outcome of women in this group. In this study we used a gene editing method to knock out, one by one, each of 198 genes that are located within the amplified region of chromosome 11 and determined how much each of these genes contributed to the survival of breast cancer cells.
View Article and Find Full Text PDFExternal Validation of a 5-Factor Risk Model for Breast Cancer-Related Lymphedema.
JAMA Netw Open
January 2025
Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Importance: Secondary lymphedema is a common, harmful side effect of breast cancer treatment. Robust risk models that are externally validated are needed to facilitate clinical translation. A published risk model used 5 accessible clinical factors to predict the development of breast cancer-related lymphedema; this model included a patient's mammographic breast density as a novel predictive factor.
View Article and Find Full Text PDFSynthesis and characterization of new (Au, Ru, and Rh) ion complexes and evaluating their activity as anticancer and antioxidants.
Appl Biochem Biotechnol
January 2025
Department of Chemistry, College of Sciences for Women, University of Baghdad, Baghdad, Iraq.
Azo dye was used to prepare a new series of complexes with chlorides of rhodium (Rh), ruthenium (Ru), and corona (Au). The prepared materials were subjected to infrared, ultraviolet-visible, and mass spectrometry, as well as thermogravimetric analysis, differential calorimetry, and elemental analysis. Conductivity, magnetic susceptibility, metal content, and chlorine content of the complexes were also measured.
View Article and Find Full Text PDFInformational Sources About Breastfeeding Associated with Breastfeeding Initiation: Insights into Racial Disparities.
Breastfeed Med
January 2025
School of Public Health, College of Public Health, University of North Texas Health Science Center, Fort Worth, Texas, USA.
Breastfeeding provides essential nutrition and disease protection for infants while reducing the risk of type 2 diabetes and breast cancer in mothers. Despite these benefits, significant racial and ethnic disparities exist in breastfeeding initiation, particularly among Black women. This study examines racial differences in the receipt of breastfeeding information from varying sources and their association with breastfeeding initiation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!