Aromatase, the enzyme responsible for estrogen biosynthesis, is a particularly attractive target in the treatment of hormone-dependent breast cancer. The synthesis and biological evaluation of a series of 2-(4'-pyridylmethyl)thio, 7-alkyl- or aryl-substituted isoflavones as potential aromatase inhibitors are described. The isoflavone derivatives demonstrate IC(50) values from 79 to 553 nM and compete with the endogenous substrate, androstenedione. Data supporting the ability of these analogs to suppress aromatase enzyme activity in the SK-BR-3 breast cancer cell line are also presented.
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http://dx.doi.org/10.1016/j.bmc.2005.07.038 | DOI Listing |
Molecules
December 2024
Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche "STEBICEF", University of Palermo, Viale delle Scienze, Ed. 17, 90128 Palermo, Italy.
Breast cancer remains one of the most prevalent and lethal malignancies in women, particularly the estrogen receptor-positive (ER+) subtype, which accounts for approximately 70% of cases. Traditional endocrine therapies, including aromatase inhibitors, selective estrogen receptor degraders/antagonists (SERDs), and selective estrogen receptor modulators (SERMs), have improved outcomes for metastatic ER+ breast cancer. However, resistance to these agents presents a significant challenge.
View Article and Find Full Text PDFCancers (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 PDFJ Obstet Gynaecol India
December 2024
Nowrosjee Wadia Maternity Hospital, Mumbai, India.
Endometriosis affects about 10 percent women in the reproductive age group globally and approximately 42 million in India. Managing the patient's pain symptoms associated with endometriosis appears to be the cornerstone in endometriosis disease management. The ideal medical treatment in endometriosis would be suppressing estradiol enough to alleviate symptoms of endometriosis but maintain sufficient levels to mitigate hypoestrogenic side effects.
View Article and Find Full Text PDFESMO Open
January 2025
Abramson Cancer Center, University of Pennsylvania, Philadelphia, USA.
Background: Concomitant intake of proton pump inhibitors (PPIs) may create drug-drug interactions, potentially impacting efficacy of anticancer agents. In the phase III PALLAS trial, the addition of palbociclib capsules to standard adjuvant endocrine therapy in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer did not improve invasive disease-free survival (iDFS). We explored whether concomitant use of PPIs affected survival outcomes in patients treated with palbociclib in PALLAS.
View Article and Find Full Text PDFESMO Open
January 2025
UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, USA.
Background: Randomized controlled trials have shown inconsistent overall survival (OS) benefit among the three cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) as first-line (1L) treatment of patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC). Several real-world studies compared CDK4/6i effectiveness, with inconsistent findings. This study compared overall survival (OS) of patients with HR+/HER2- mBC receiving 1L palbociclib, ribociclib, or abemaciclib, in combination with an aromatase inhibitor (AI), in US clinical practice.
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