Abstract
Although TNF antitumor activity has been demonstrated in many preclinical models and in non-comparative clinical trials, no evidence exists that TNF-based treatments increase patient survival. Moreover, due to systemic toxicity, TNF can only be administered through sophisticated locoregional drug-delivery systems in patients with some types of organ-confined solid tumors; as a corollary, the impossibility to administer TNF through the systemic route does not allow to test the effectiveness of this cytokine in other clinical settings for the treatment of a broader spectrum of tumor types. A challenge many researchers are tackling is to dissect the cascade of molecular events underlying tumor sensitivity to TNF so to fully explore the anticancer potential of this molecule. The rationale for the development of strategies aimed at sensitizing malignant cells to TNF is to exploit tumor-specific molecular derangements to modulate TNF biological activities and ultimately maximize its tumor-selective cytotoxicity. This would not only enhance the anticancer activity of current TNF-based locoregional regimens, but would also open the avenue to the systemic administration of this cytokine and thus to a much wider clinical experimentation of TNF in the oncology field. In this review we first summarize the molecular biology of TNF and its cancer-related properties; then, the available findings regarding some among the most promising and best characterized TNF sensitizers are overviewed.
Keywords: Tumor necrosis factor (TNF), molecular biology, cancer, apoptosis, angiogenesis, cancer therapy, drug resistance, drug synergism, sensitizing agents
Current Pharmaceutical Design
Title: Towards the Development of Tumor Necrosis Factor (TNF) Sensitizers:Making TNF Work Against Cancer
Volume: 13 Issue: 5
Author(s): Simone Mocellin, Pierluigi Pilati and Donato Nitti
Affiliation:
Keywords: Tumor necrosis factor (TNF), molecular biology, cancer, apoptosis, angiogenesis, cancer therapy, drug resistance, drug synergism, sensitizing agents
Abstract: Although TNF antitumor activity has been demonstrated in many preclinical models and in non-comparative clinical trials, no evidence exists that TNF-based treatments increase patient survival. Moreover, due to systemic toxicity, TNF can only be administered through sophisticated locoregional drug-delivery systems in patients with some types of organ-confined solid tumors; as a corollary, the impossibility to administer TNF through the systemic route does not allow to test the effectiveness of this cytokine in other clinical settings for the treatment of a broader spectrum of tumor types. A challenge many researchers are tackling is to dissect the cascade of molecular events underlying tumor sensitivity to TNF so to fully explore the anticancer potential of this molecule. The rationale for the development of strategies aimed at sensitizing malignant cells to TNF is to exploit tumor-specific molecular derangements to modulate TNF biological activities and ultimately maximize its tumor-selective cytotoxicity. This would not only enhance the anticancer activity of current TNF-based locoregional regimens, but would also open the avenue to the systemic administration of this cytokine and thus to a much wider clinical experimentation of TNF in the oncology field. In this review we first summarize the molecular biology of TNF and its cancer-related properties; then, the available findings regarding some among the most promising and best characterized TNF sensitizers are overviewed.
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Cite this article as:
Mocellin Simone, Pilati Pierluigi and Nitti Donato, Towards the Development of Tumor Necrosis Factor (TNF) Sensitizers:Making TNF Work Against Cancer, Current Pharmaceutical Design 2007; 13 (5) . https://dx.doi.org/10.2174/138161207780162926
DOI https://dx.doi.org/10.2174/138161207780162926 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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