These findings suggest that coordinated targeting of proteostasis, checkpoint axis regulation, and TLR7 signaling not only dismantles EGFR-driven oncogenic survival circuitry but also reshapes the TME into a niche favoring T cell recruitment and immune activation, providing a mechanistically substantiated strategy to surmount immunotherapy resistance in MSS CRC. The gene discussed is EGFR; the disease is colorectal carcinoma.