Pharmacologic reprogramming of virus-tumor crosstalk enhances measles virus antitumor activity in BRAF mutant colorectal cancer models - PubMed
5 hours ago
- #oncolytic virotherapy
- #BRAF mutation
- #colorectal cancer
- Combining triptolide or its prodrug Minnelide with oncolytic measles virus (MV) enhances virus-mediated cancer cell killing in colorectal cancer (CRC), especially in BRAF V600E mutant models.
- In vitro, triptolide improves MV oncolysis in CRC cell lines and modulates pathways like AKT, apoptosis, and metabolism.
- In vivo, Minnelide boosts the efficacy of systemically administered MV-CD46-muPA in xenografts, with stronger effects in BRAF mutant HT29 tumors.
- The combination therapy reprograms virus-tumor-stromal interactions, affecting cell cycle, metabolism, survival genes, and increasing apoptosis.
- Enhanced outcomes include reduced tumor proliferation (Ki67), decreased angiogenesis (CD31), improved intratumoral viral distribution, and increased apoptosis (TUNEL).
- Findings support virus-drug combinations as a strategy to overcome resistance and improve virotherapy in CRC and other cancers.