ESR1 mutation

P1/2, N=65, Recruiting, Sarah Sammons, MD | Not yet recruiting --> Recruiting | Initiation date: Mar 2026 --> Nov 2025

This switch-blocker-enhanced pyrosequencing assay presents a targeted, multiplexed, and accessible approach for detecting ESR1 hotspot mutations in liquid biopsies. This assay has potential for dynamic monitoring of therapeutic resistance, facilitating timely treatment decisions in advanced breast cancer management.

Moreover, we identified PR-dependent transcriptional programs such as the unfolded protein response (UPR) that can be leveraged to target CSCs in Y537S ESR1-mutant breast cancer. Our findings demonstrate an interplay between PR and mutant ER function and provide insight into PR-driven pathways that can be exploited as potential therapeutic avenues in ER+ breast cancer.

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