Abraham

Most locally advanced rectal cancers are mismatch-repair proficient and have no molecularly-guided treatment. We asked whether drugs that already exist could help, guided by the biology that makes these tumors resist chemoradiation. Anchoring to the chemoradiation-resistance gene program (GSE209746), two independent engines — one by drug target, one by measured kinase binding — nominated 287 clinically-available drugs. A permutation test confirmed the anchor is non-arbitrary (p=0.001 vs 1,000 random gene sets). FDA-label safety filtering distilled this to two ranked shortlists of 44 drugs, ready for patient-derived organoid testing. Claude drove the full scientific method: planning, building both engines, integrating eleven public databases, reasoning through methodology, drafting the manuscript, then acting as a critical peer reviewer that exposed weak claims — which we revised into a stronger, defensible result. One researcher, the complete arc of science.