Abstract
BACKGROUND: Colorectal cancer (CRC), encompassing both colon and rectal carcinogenesis, is a major health concern. Metastatic CRC (mCRC) is the third most common cancer and the second leading cause of cancer-related death in United States adults. Despite advances in therapy, the 5-year survival rate remains low at 15%. KRAS mutations contribute to treatment resistance by altering the tumor microenvironment, necessitating novel therapeutic approaches. AIM: To evaluate immunomodulatory and cytotoxic potential of reovirus as an adjuvant therapy in KRAS-mutant-mCRC patients by analyzing gene and cytokine expression. METHODS: Five KRAS-mutant mCRC patients were treated with reovirus. Serum samples were collected at five time points over 15 days. Cytokine levels were measured using enzyme-linked immunosorbent assay, and transcriptomic profiling was performed to assess gene expression. Data were analyzed using the 2(-ΔΔCt) method, and statistical significance was determined via two-tailed t-tests (P < 0.05). RESULTS: Out of 271 genes associated with Janus kinase/signal transducer and activator of transcription, Ras, Wnt, and phosphoinositide 3-kinase- alpha serine/threonine-protein kinase pathways, 85 showed significant modulation. Additionally, 17 of 25 cytokines were significantly altered. Reovirus induced changes in both gene and cytokine expression, suggesting activation of a complex intracellular signaling network. CONCLUSION: Reovirus demonstrates potential as an immunomodulatory and cytotoxic adjuvant in KRAS-mutant mCRC by altering key signaling pathways and cytokine profiles. These findings support further investigation into its potential therapeutic contributions.