p110α is an important subunit of phosphatidylinositol-3-kinases (PI3Ks) encoded by . Though PI3Ks are known as crucial regulators of cellular growth and proliferation, the function of mutations in fulvestrant resistance remains elusive. Thus, this study aimed to investigate the roles of mutations in fulvestrant resistance and tumor progression. Using circulating tumor DNA (ctDNA) from four fulvestrant-resistant patients, we found three of them were mutated, one with a novel mutation (p.R115P). experiments further evaluated the functions of those mutations and underlying mechanisms. We identified mutations could not only confer to fulvestrant resistance, but also promote cell proliferation and migration. Inhibition of corresponding activated pathways could effectively suppress cell growth.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789267 | PMC |
Publication Analysis
Top Keywords
Similar Publications
Oral selective estrogen receptor degraders for breast cancer treatment: focus on pharmacological differences.
Breast Cancer Res Treat
January 2025
Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology IRCCS, Milan, Italy.
Purpose: The management of hormone receptor-positive (HR +) breast cancer (BC) relies on endocrine therapy (ET), with a primary focus on disrupting estrogen receptor (ER) signaling due to its critical role in BC tumorigenesis and progression. While effective for both early-stage and advanced breast cancers, ET frequently encounters resistance mechanisms, including both ligand-dependent and ligand-independent trajectories, ultimately leading to disease progression.
Methods: We searched PubMed, EMBASE and Scopus databases to review the current evidence on the use of novel oral selective estrogen receptor degraders (SERDs) for the treatment of HR+ BC.
Fulvestrant Monotherapy After CDK4/6 Inhibitors in Metastatic Breast Cancer Patients: A Real-Life Experience.
Cancers (Basel)
December 2024
Breast and Gyncological Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.
The treatment of hormone receptor positive (HR+), HER-2 negative metastatic breast cancer (MBC) has radically changed over the last few years. CDK4/6 inhibitors combined with endocrine therapy have become the standard of care as a front-line therapeutic approach, conferring a significant improvement in progression-free survival and overall survival compared to traditional endocrine therapy (ET) alone. However, the wide administration of these drugs in clinical practice paved the way for the emergence of new intrinsic and acquired mechanisms of resistance that seem to compromise second-line treatment effectiveness.
View Article and Find Full Text PDFMetabolic Switch in Endocrine Resistant Estrogen Receptor Positive Breast Cancer.
bioRxiv
December 2024
Department of Medicine, Division of Medical Oncology, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado USA.
Purpose: The development of endocrine resistance remains a significant challenge in the clinical management of estrogen receptor-positive () breast cancer. Metabolic reprogramming is a prominent component of endocrine resistance and a potential therapeutic intervention point. However, a limited understanding of which metabolic changes are conserved across the heterogeneous landscape of ER+ breast cancer or how metabolic changes factor into ER DNA binding patterns hinder our ability to target metabolic adaptation as a treatment strategy.
View Article and Find Full Text PDFMolecular Profiling of Endocrine Resistance in HR+/HER2-Metastatic Breast Cancer: Insights from Extracellular Vesicles-Derived DNA and ctDNA in Liquid Biopsies.
Int J Mol Sci
December 2024
"Clinical and Translational Research in Oncology" Group, Molecular Oncology Laboratory, Hospital Clinico San Carlos, Instituto de Investigación Sanitaria Hospital Clinico San Carlos (IdISSC), 28040 Madrid, Spain.
Standard treatments in hormone receptor-positive (HR+)/HER2-metastatic breast cancer (mBC) typically involve endocrine therapy (ET) combined with CDK4/6 inhibitors, yet resistance to ET remains a persistent challenge in advanced cases. A deeper knowledge of the use of liquid biopsy is crucial for the implementation of precision medicine in mBC with real-time treatment guidance. Our study assesses the prognostic value of and mutations in DNA derived from extracellular vesicles (EV-DNA) in longitudinal plasma from 59 HR+/HER2-mBC patients previously exposed to aromatase inhibitors, with a comparative analysis against circulating tumor DNA (ctDNA).
View Article and Find Full Text PDFPractical treatment strategies and novel therapies in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) advanced breast cancer.
ESMO Open
December 2024
Medical Oncology, Dana-Farber Cancer Institute, Boston, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, USA; Harvard Medical School, Boston, USA. Electronic address:
Mutations in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway occur in 30%-40% of patients with advanced hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) breast cancer. For most patients, endocrine therapy with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor is the first-line treatment. Recent studies indicate that adding inavolisib, a PI3Kα inhibitor, to palbociclib/fulvestrant benefits patients with endocrine-resistant HR+/HER2- metastatic breast cancer with a PIK3CA mutation.
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!