Abstract B142: EO3001: A novel agent for ARID1A mutant cancers
Bibliographic record
Abstract
Abstract Background ARID1A mutations are among the most common genetic alterations in cancer, occurring in approximately 65% of ovarian clear cell carcinoma (OCCC) and up to 10% of all solid tumors. These mutations disrupt chromatin remodeling and cellular homeostasis, leading to the accumulation of reactive oxygen species (ROS) and a metabolic shift that renders tumor cells increasingly dependent on oxidative phosphorylation (OXPHOS) for survival. This metabolic vulnerability provides a therapeutic opportunity for selective targeting. EO3001 is a novel synthetic agent that transports extracellular Cu(II) to mitochondria, promoting mitochondrial ROS generation and triggering cancer cell death. Preclinical studies have shown that EO3001 exhibits selective cytotoxicity in ARID1A-deficient CCOC models, highlighting its potential as a precision oncology candidate. Methods To evaluate EO3001’s activity, isogenic CCOC cell lines with and without ARID1A expression were generated using CRISPR-Cas9 gene editing. The compound’s effects were assessed through a series of in vitro and ex vivo assays, measuring cell viability, mitochondrial ROS levels, OXPHOS activity, and invasive potential under various metabolic stress conditions. Notably, EO3001 demonstrated robust anti-tumor activity in ARID1A-deficient cells, with markedly reduced efficacy in hypoxic environments—supporting the mechanism of action linked to OXPHOS dependence. Conclusions and Next Steps These findings suggest that EO3001 holds promise as a targeted therapeutic for ARID1A-mutant cancers, and ongoing work is focused on optimizing its application in clinically relevant settings. A biomarker-driven clinical trial is planed to further evaluate these findings. Citation Format: Jeffrey Bacha, Yuchen Ding, Dennis Brown, Amal M. El-Naggar, David G. Huntsman, Sarath Kanekal, Neil Sankar. EO3001: A novel agent for ARID1A mutant cancers [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr B142.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".