Oncology

Modulating autophagy in KRAS mutant colorectal cancer using combination of oncolytic reovirus and carbamazepine

Ethan Littlefield

25 Jun 2025 — 1 min read

PMCID: PMC12173229

PMID: 40526688

DOI: 10.1371/journal.pone.0326029

Journal: PloS one

Publication Date: 2025-6-17

Authors: Shaykevich A, Chae D, Silverman I, Goel S, Maitra R

Key Points

Carbamazepine and oncolytic reovirus demonstrate synergistic effects in inducing autophagy in KRAS-mutated colorectal cancer cells
Dual treatment significantly increased autophagy-related protein expression (p < 0.001 for multiple proteins at 6h and 24h)
Combination therapy offers a targeted approach for KRAS-mutated colorectal cancer with enhanced autophagic cell death

Summary

This preclinical study investigated a novel combination therapy for colorectal cancer patients with KRAS mutations, exploring the synergistic potential of oncolytic reovirus and carbamazepine in enhancing autophagy-mediated cancer cell death. The research focused on how these agents interact specifically in KRAS-mutated cell lines, demonstrating that the dual treatment significantly increases autophagy-related protein expression and autophagosome formation compared to individual treatments.

The study revealed that the combination of carbamazepine and reovirus preferentially targets KRAS-mutated colorectal cancer cells by dramatically upregulating key autophagy proteins and genes. Transmission electron microscopy confirmed increased autophagosome formation, with the dual treatment showing a synergistic effect that was more pronounced in KRAS-mutant cells compared to wild-type cells. These findings suggest a promising therapeutic approach that could potentially improve treatment outcomes for patients with KRAS-mutated colorectal cancer.

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