To test this hypothesis, we treated MCF-7 and T47D ER-positive breast cancer cells with 17-β-estradiol (E2), either alone or in combination with selective ERα antagonist AZD9496, selective ERβ antagonist PHTPP, DNA methyltransferase (DNMT) inhibitor RG108, and selective ER degrader Fulvestrant (Ful). RG108 strengthened UV-C-induced pyroptosis, and Ful reversed the inhibitory effects of E2 on UV-C-induced pyroptosis of MCF-7 and T47D cells. Taken together, our study suggests that E2 down-regulated GSDME expression in ERα-positive breast cancer by promoting GSDME promoter methylation, and inhibited UV-C-induced pyroptosis.

This meta-analysis reinforces the importance of molecular stratification in treatment decisions after CDK4/6i progression, highlighting the need for efficacy and safety assessments across biomarker-selected subgroups.

Fulvestrant, a selective estrogen receptor degrader (SERD) that antagonizes and degrades ER simultaneously, has demonstrated activity in ER+/HER2- breast cancers the ability to overcome endocrine resistance. These data support the clinical utility of ZN-c5 as monotherapy and as a combination therapy for patients with ER+/HER2- breast cancers. While encouraging plasma exposure and tolerability have been observed for ZN-c5 in patients, further studies are needed to optimize its therapeutic efficacy.

P1, N=16, Active, not recruiting, Shandong Suncadia Medicine Co., Ltd. | Not yet recruiting --> Active, not recruiting

This study systematically reveals that EDCs promote HCC initiation and progression by perturbing cell cycle, metabolic, and immune homeostasis through multi-target, multi-pathway mechanisms. The nine-gene risk model demonstrates superior performance in HCC diagnosis and prognosis and shows potential clinical translational value in drug-sensitivity prediction and pan-cancer analyses. This work provides a new perspective at the intersection of environmental toxicology and precision oncology and informs individualized therapeutic strategies.

P3, N=240, Active, not recruiting, MedSIR | Recruiting --> Active, not recruiting

Capivasertib, an AKT inhibitor, approved in combination with fulvestrant for hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer with ≥1 PIK3CA, AKT1, and/or PTEN alterations, significantly improved progression-free survival in the CAPItello-291 phase 3 trial. However, capivasertib-associated adverse events of diarrhea, rash, and hyperglycemia may require proactive management. This article provides practical recommendations to support prevention and early intervention to optimize adherence and treatment outcomes.

Propylparaben may promote the occurrence and progression of estrogen receptor-positive breast cancer by upregulating SLC2A1 and KIF11, activating metabolic and proliferative pathways, and simultaneously suppressing tumor-suppressive signals.

Patients with ER+ HER2- ABC in this study preferred oral to IM ET owing to convenience, and disliked the pain associated with IM ET and travel to receive injections. Compared to IM fulvestrant, oral SERDs may offer an alternative with less burden on the lives of people living with cancer.

Early clinical data demonstrated activity of BLU-222, a potent and selective CDK2 inhibitor, both as monotherapy (CCNE1 amplified) and in combination with ribociclib and fulvestrant in patients with HR+/HER2- breast cancer. These findings provide evidence that CDK2i combined with CDK4/6i can address multiple known mechanisms of resistance to CDK4/6i, enhancing antitumor responses in preclinical breast cancer models.

In September 2025, imlunestrant was approved for the treatment of adults with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy in the USA. This article summarizes the milestones in the development of imlunestrant leading to this first approval for use in patients with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer.

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