Drug Repurposing Candidates for Triple-Negative Breast Cancer
Discover (after iteration 10) — find something NEW that iteration 10 did not establish about the research question: a pattern, mechanism, candidate or effect that no published work reports. Start from what is still open: Derive a TNBC-vs-luminal expression signature on TCGA-BRCA, validate it on METABRIC, and score approved drugs by perturbation-signature reversal; Compute TNBC-selective CRISPR dependencies across all genes, not only metabolic ones, and match them to targets of approved non-oncology drugs; Label breast lines by ER/PR/HER2 expression and validate against known TNBC lines. Rerun the PRISM analysis with AUC values, adding CTRP/GDSC replication and a basal-like vs mesenchymal check; Rank drugs by agreement across the three approaches, exclude those already studied via literature and trial registries, and repeat the lipophilicity test matched on target class; Name the six metabolic hits and map them to approved drugs. Within the research question, generate the data, state one precise claim, test it on data or cases not used to find it, try to break it, and check its novelty against the literature.
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