Estrogen Receptor Positive Breast Cancer

Comprehensive CYP2D6 profiling improves phenotype assignment and highlights methodological pitfalls that may contribute to inconsistencies in pharmacogenetic studies. While no definitive association with clinical outcomes was observed in the overall cohort, these findings underscore the importance of analytically robust genotyping strategies and warrant validation in larger, prospectively designed cohorts, and highlight the importance of comprehensive genotyping strategies in resolving inconsistencies across pharmacogenetic studies.

P=N/A, N=216, Completed, Haydarpasa Numune Training and Research Hospital

Thus, VALD-3 treatment initiated the ROS/JNK/Bax-mitochondrial apoptosis pathway, leading to caspase-3 activation and GSDME cleavage, thereby executing pyroptosis. These findings suggest that GSDME-dependent pyroptosis is a novel mechanism by which VALD-3 eradicates cancer cells and offer new insights into potential clinical applications for anticancer therapies.

P=N/A, N=1500, Not yet recruiting, Hunan Cancer Hospital

P=N/A, N=180, Not yet recruiting, Ankara University

P2, N=48, Active, not recruiting, City of Hope Medical Center | Trial completion date: Jun 2026 --> May 2027 | Trial primary completion date: Jun 2026 --> May 2027

P=N/A, N=2295, Recruiting, Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company | N=1155 --> 2295 | Trial completion date: Sep 2028 --> Dec 2030 | Trial primary completion date: Sep 2028 --> Dec 2030

Cells were characterized for dormancy- like behavior using increased p-p38 and decreased p-ERK expression (dormant, p-p38High and p-ERKLow expression), reduced Ki67 expression, elevated p21 and p27 levels by immunofluorescence, absence of senescence using β-galactosidase staining and resistance to doxorubicin...FGF-2 was required with laminin to induce dormancy in MDA-MB-231 cells under hypoxic conditions (FGF-2 plus fibronectin were unable to induce dormancy), whereas laminin or fibronectin alone were sufficient under normoxic conditions. Overall, we established culture conditions that recapitulate an in vitro breast cancer dormancy-like phenotype and reveal subtype-specific differences in dormancy regulation.

High-resolution lineage tracing and multi-omic studies demonstrate that CDK4/6i resistance is shaped by clonal selection and adaptive remodeling of cell states, with the ESR1 mutation status and the specific inhibitor acting as key determinants of evolutionary trajectories. These findings suggest that both variables should be considered when designing sequential and combination treatment strategies to overcome CDK4/6i resistance.

siRNA-mediated knockdown of LXR expression only partially recapitulated the actions of 1E5, suggesting the involvement of LXR-dependent and independent mechanisms. Collectively, these findings reveal potential crosstalk between LXR and the genetic and epigenetic regulation of pathways involved in endocrine response and alternative signaling mechanisms, highlighting potential targets in endocrine-resistant breast cancer.

The combination of PLD with pembrolizumab is well tolerated, active, and feasible for extended treatment with durable responses. The results suggest possible contribution of pembrolizumab to the anti-tumor effect.

P=N/A, N=100, Completed, UNC Lineberger Comprehensive Cancer Center | Recruiting --> Completed | N=240 --> 100