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Tumour necrosis factor and cancer
1Imperial Cancer Research Fund, London, U.K.
Progress in Growth Factor Research
|January 1, 1992
Summary
Tumor necrosis factor (TNF) has a dual role in cancer, potentially aiding therapy or promoting progression. Localized TNF therapy shows promise for tumor regression, but systemic use is toxic.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Tumor necrosis factor (TNF) is a cytokine with complex roles in inflammation and immunity.
- Its involvement in cancer includes potential therapeutic benefits and contributions to malignant progression.
Purpose of the Study:
- To explore the multifaceted role of TNF in cancer, encompassing both therapeutic potential and disease progression.
- To evaluate the efficacy and toxicity of systemic versus local TNF administration in cancer treatment.
Main Methods:
- Review of preclinical data and clinical trial outcomes for TNF-based cancer therapies.
- Analysis of experimental models demonstrating TNF's effects on tumor vasculature and immunity.
- Investigation of TNF's autocrine/paracrine signaling in human ovarian cancer.
Main Results:
- Systemic TNF therapy in human cancer has shown high toxicity and limited efficacy.
- Local TNF administration, specifically isolated limb perfusion, achieved complete and durable tumor regressions.
- TNF can induce tumor-specific vascular necrosis and immunity in experimental models.
- Evidence suggests TNF contributes to malignant progression in animal models and may act in human ovarian cancer.
Conclusions:
- TNF exhibits a context-dependent role in cancer, influencing both host defense and tumor progression.
- Local administration of TNF offers a promising therapeutic strategy with manageable toxicity and significant anti-tumor activity.
- Further research is warranted to elucidate TNF's precise mechanisms in different cancer types and optimize its therapeutic application.