World J Clin Oncol. 2026 Feb 24;17(2):113428. doi: 10.5306/wjco.v17.i2.113428.
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.
PMID:41810348 | PMC:PMC12968548 | DOI:10.5306/wjco.v17.i2.113428
