Strategies to enhance the anticancer potential of TNF.
Although tumor necrosis factor (TNF) antitumor activity is evident in several preclinical models and in non-comparative clinical trials, no evidence exists that TNF-based treatments increase patient survival. Furthermore, due to systemic toxicity, TNF can only be administered via sophisticated drug-delivery systems in patients with solid tumors confined to one extremity or organ. The impossibility to administer TNF systemically does not allow to test the effectiveness of this cytokine in other clinical settings for the treatment of a broader spectrum of tumor types. Dissecting the cascade of molecular events underlying tumor sensitivity to TNF researchers will allow to further exploit the anticancer potential of this molecule. The rational for the development of strategies aimed at sensitizing malignant cells to TNF is to modulate tumor-specific molecular derangements in order to maximize the selectivity of TNF cytotoxicity towards cancer. This would enhance the anticancer activity of current TNF-based locoregional regimens and would pave the way to the systemic administration of this cytokine and thus to a much wider clinical experimentation of TNF in the oncology field.
Pilati
Pierluigi
P
Department of Oncological and Surgical Sciences, University of Padova, via Giustiniani 2, 35128 Padova, Italy.
Rossi
Carlo Riccardo
CR
Mocellin
Simone
S
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation; D002470:Cell Survival; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D008495:Medical Oncology / Q000379:methods; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy; D009569:Nitric Oxide / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide