letrozole

MTT assay showed that 6 and 9b were 4.5 and 2 times more potent than doxorubicin against MCF-7 cells, while 9a and 13b were 10 and 7.5 times more effective against MDA-MB-231 cells, respectively...Compound 13b exhibited comparable EGFRL858R inhibition to lapatinib and outperformed pictilisib against PI3Kα, PI3Kβ, and PI3Kδ. Compound 6 showed greater ARO inhibition than letrozole, while being slightly less potent than pictilisib against PI3Kα and PI3Kβ...Docking studies supported the in vitro enzymatic inhibition assays results. Thus, 9b and 13d are potent anti-breast cancer benzoxazoles with selective ARO and PI3kα inhibition activity, respectively, while 6, 9a, and 13b are multi-target inhibitors exhibiting other anticancer synergistic mechanisms.

Based on preclinical studies showing synergism with simultaneous inhibition of the estrogen receptor (ER), CDK4/6 and PI3K pathways and based on window of opportunity studies showing that metformin suppresses PI3K/mTOR signaling in endometrial cancer (EC), we conduct a non-randomized phase 2 study of letrozole/abemaciclib/metformin in ER positive endometrioid EC (NCT03675893). There are no objective responses among TP53 mutated ECs and among NSMP (no specific molecular profile) tumors with RB1 or CCNE1 alterations; CTNNB1 mutations correlate with clinical benefit. Pharmacokinetic analyses demonstrate that administration of letrozole and abemaciclib with metformin result in a more than 3-fold increase in metformin exposure.

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

PIP mRNA expression and specific immune-stromal features are associated with resistance to EVE. These findings suggest the potential of PIP as a spatially resolved predictive biomarker for patient stratification in HR+/HER2- ABC.

This prespecified 5-year follow-up of efficacy outcomes from NATALEE demonstrated that ribociclib + NSAI continued to reduce the risk of recurrence beyond the 3-year treatment window, supporting its use as adjuvant therapy in patients with HR-positive/HER2-negative EBC. An ongoing positive trend for improved OS in favor of ribociclib + NSAI was observed.

The three phytochemicals identified from Ricinus communis show promise as novel aromatase inhibitors with superior binding and favorable pharmacokinetic predictions compared to Letrozole. These compounds warrant further in vitro and in vivo study as potential breast cancer therapeutics.

P1/2, N=792, Recruiting, Hoffmann-La Roche | N=580 --> 792 | Trial completion date: May 2028 --> Sep 2030 | Trial primary completion date: May 2028 --> Sep 2030

The patient developed a grade 3 eruptive, maculopapular dermatitis to exemestane and subsequently letrozole. Unusually, a third AI - anastrozole - has been well tolerated. Severe dAEs secondary to AIs are rare, and there is a lack of evidence-based research to guide management of these reactions.

Combinatorial effects with hormone therapies (tamoxifen, fulvestrant, and letrozole) and the AKT inhibitor MK2206 were evaluated. Xanthene- and pyran-based hybrids-particularly SJ028, SJ064, and SJ078-showed strong antitumor activity through apoptosis induction, cell cycle arrest, and PI3K/AKT pathway modulation. Their preserved efficacy in resistant models and synergistic interactions with hormone therapies contrasted with the antagonism observed with AKT inhibition, highlighting their potential as promising candidates for the treatment of hormone-responsive and -resistant cancers.

P2, N=35, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting

P=N/A, N=1, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | N=5087 --> 1

This study shows that BSHT dose-dependently activates the PI3K/Akt pathway, inhibits GSDMD-mediated pyroptosis, and improves mitochondrial dysfunction in PCOS. Its regulation of inflammation, oxidative stress, metabolism, and ovarian function suggests a promising multi-target therapeutic strategy and provides insights for future clinical applications.