TNF: A Tumor-Suppressing Factor or a Tumor-Promoting Factor?

Evaluation of: Cordero JB, Macagno JP, Stefanatos RK, Strathdee KE, Cagan RL, Vidal M: Oncogenic Ras diverts a host TNF tumor suppressor activity into tumor promoter. Dev. Cell 18, 999–1011 (2010). TNF-α is a major inflammatory cytokine named for its ability to induce rapid hemorrhagic necrosis of experimental cancers. During efforts to harness this antitumor activity in cancer treatments in the 1980s, a paradoxical tumor-promoting role of TNF became apparent. The cellular and molecular complexity of mammalian tumor microenvironments makes these opposing effects difficult to study. The fruit fly Drosophila melanogaster provides a simpler model system for studying complex cellular and genetic interactions that lead to tumor formation and progression. The paper from Marcos Vidal’s group shows that both the tumor-suppressing and tumor-promoting roles of TNF are conserved in Drosophila, and that oncogenic Ras is the switch. The links between inflammation and cancer are now more fully understood, but it is still not clear whether TNF has potential as a target or a therapeutic in malignant disease, or both. Research in an invertebrate organism may provide important insights.