To investigate the antitumor effects of sertraline in colon cancer, particularly its impact on MEK/ERK signaling and tumor growthTo explore the role of sertraline in colon tumorigenesis using SERT‐knockout miceTo evaluate whether combining SERT with trametinib or a tryptophan‐restricted diet enhances antitumor efficacy via inhibition of the MEK/ERK pathway. Here, SLC6A4 is linked to neoplasm.