Given the enhanced activity of 8-Nitrotryp in other cancers and the critical role of TGF-β/SMAD and PI3K/AKT/mTOR signaling in CRC progression across molecular subtypes, we hypothesized that 8-Nitrotryp exerts potent antitumor effects against CRC by inhibiting these key oncogenic pathways and suppressing associated processes like EMT. Here, PIK3CA is linked to cancer.