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TNF blockade: an inflammatory issue
B B Aggarwal1, S Shishodia, Y Takada
1Cytokine Research Laboratory, Department of Experimental Therapeutics, University of Texas, M.D. Anderson Cancer Hospital 77030, USA. aggarwal@mdanderson.org
Ernst Schering Research Foundation Workshop
|December 8, 2005
Summary
Tumor necrosis factor (TNF) plays a dual role in cancer and inflammation. New safe and effective TNF-targeting therapies are needed, potentially from natural sources, to balance its beneficial immune functions with its harmful effects.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Tumor necrosis factor (TNF) has a complex role, mediating tumor progression and various inflammatory diseases.
- TNF is crucial for immune surveillance and the function of immune cells like NK, T, B cells, macrophages, and dendritic cells.
- Current TNF inhibitors (e.g., Remicade, Humira, Enbrel) alleviate inflammatory symptoms but increase risks of infections, cancers, and cardiotoxicity.
Purpose of the Study:
- To address the urgent need for safe and effective TNF-targeting therapeutics.
- To explore the differential roles of transmembrane versus soluble TNF.
- To identify agents that can selectively modulate TNF expression or signaling pathways.
Main Methods:
- Review of existing literature on TNF's role in disease and immunity.
- Analysis of TNF signaling pathways (caspases, NF-kappaB, AP-1, MAPKs).
- Identification of natural product-derived agents with potential to regulate TNF.
Main Results:
- TNF is implicated in tumor initiation, promotion, and metastasis.
- Dysregulated TNF is linked to numerous inflammatory and autoimmune diseases.
- Evidence suggests transmembrane TNF may be beneficial, while soluble TNF mediates toxicity.
- TNF blockade carries significant risks, highlighting the need for safer alternatives.
- Natural agents have been identified that may differentially regulate TNF.
Conclusions:
- Developing therapeutics that selectively target TNF pathways is critical for managing inflammatory diseases and cancer.
- Future therapies should aim to harness beneficial TNF functions while mitigating toxic effects.
- Natural product-derived agents represent a promising avenue for discovering novel, safer TNF modulators.