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 machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".