These findings establish 8-Nitrotryp as a promising therapeutic candidate, warranting further evaluation through nanoparticle-based delivery systems to enhance bioavailability, validation across heterogeneous CRC cell lines (including mesenchymal and chemoresistant subtypes), efficacy assessment in patient-derived xenograft and metastatic animal models, and exploration of clinical applications for TGF-β/PI3K-hyperactivated CRC. The gene discussed is PIK3CA; the disease is colorectal carcinoma.