ESR1 mutation

Off-the-shelf general-purpose LLMs in a fixed retrieval pipeline were able to abstract a range of variables from complex longitudinal oncology records with performance approaching inter-oncologist variability for key tasks, without any fine-tuning or institution-specific retraining. This approach offers a practical path to scaling the creation of research-grade retrospective datasets from narrative medical records.

P3, N=256, Active, not recruiting, Laekna Limited | Recruiting --> Active, not recruiting

Our findings demonstrate that integrating baseline ctDNA-derived TFx metrics with established clinical variables significantly improves risk stratification in HR-positive/HER2-negative ABC.

In recent clinical trials of metastatic ER+ BC, next-generation SERDs demonstrated clinical activity, and elacestrant received an approval for advanced ESR1-mutant disease. NR tumors instead up-regulate multiple ERα-independent proliferative pathways, such as EGFR/MAPK and Hippo/TEAD, which may represent targetable dependencies in NR disease. Modeling resistance and lineage plasticity in vitro, we find that giredestrant-resistant ER+ BC cell lines exhibit profound shifts in chromatin accessibility, with the transcription factors, FOXA1 and FOXM1, implicated in gene expression of NR-upregulated proliferative pathways.

On June 6, 2025, Arvinas and Pfizer submitted a New Drug Application (NDA) for vepdegestrant to the U.S. Food and Drug Administration (FDA), representing an important step in the clinical translation of PROTAC technology. This review summarizes the design, synthesis, degradation mechanism, preclinical pharmacology, and clinical development of vepdegestrant and discusses the broader implications and future prospects of oral PROTAC-based ER degraders in breast cancer therapy.

P1/2, N=49, Completed, Carrick Therapeutics Limited | Active, not recruiting --> Completed

P3, N=510, Recruiting, Olema Pharmaceuticals, Inc. | N=370 --> 510

Furthermore, early ctDNA clearance identifies responding patients, and the combination of low ER activity and high ctDNA burden predicts rapid clinical progression. These findings provide a framework for personalizing future breast cancer therapies by integrating liquid biopsies with tissue-based signatures.

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

In concordance, validation on ESR1mut patient tumors shows decreased IL-17a and IL-1β. Collectively, our findings reveal that ESR1 mutations contribute to an immunosuppressive tumor microenvironment by dampening cytokine secretion and immune cell activity.