AI-Driven Scientific Prompting and Sequential Discovery Pipeline for NF-κB–Targeted Predictive Modeling and Therapeutic Insights in Breast Cancer Using Quercetin from Moringa oleifera

Abstract

With around 2.3 million new cases in 2020, breast cancer is the most prevalent cancer globally, and current treatments frequently fail because of inherent heterogeneity and adaptive resistance. In breast cancers, inflammation-driven NFκB signaling is substantially active, promoting cell survival, metastasis, and resistance to treatment. A naturally occurring flavonol, quercetin possesses a wide range of anti-inflammatory, antioxidant, and anti-cancer properties, including the ability to suppress NF-κB. However, quercetin's quick metabolism and low bioavailability limit its therapeutic application. A natural source of quercetin and associated compounds, Moringa oleifera requires strict standardization (HPLC/TLC fingerprinting) for reproducible research due to its high batch-to-batch variability. An AI-driven sequential discovery pipeline to speed up drug development is presented in this paper, which also summarizes preclinical data on quercetin's modulatory effects and NF-κB in breast cancer.We describe: (A) advanced literature mining and prompt engineering strategies; (B) building a knowledge graph that links nodes of the NF-κB pathway, breast cancer hallmarks, quercetin chemistry, and assay endpoints; (C) network pharmacology and causal inference for mechanism prioritization; (D) predictive modeling (QSAR/docking/transcriptomic matching); (E) virtual screening against NF-κB targets (e.g., IKKβ, p65 DNA-binding); (F) lead optimization (balancing potency, ADME, and safety); and (G) an experimental validation roadmap from biochemical assays to in vivo models with defined decision-gates. We use trust-layer knowledge graphs to address bias sources, reproducibility issues, and auditing of AI results. Lastly, we identify important gaps and future approaches, such as clinical PK/PD of quercetin, validated NF-κB biomarkers, and standardization of Moringa extracts.