Hundsberger Harald, Verin Alexander, Wiesner Christoph, Pflüger Maren, Dulebo Alexander, Schütt Wolfgang, Lasters Ignace, Männel Daniela N, Wendel Albrecht, Lucas Rudolf
Medical and Pharmaceutical Biotechnology, University of Applied Sciences, Krems, Austria.
Front Biosci. 2008 May 1;13:5374-86. doi: 10.2741/3087.
The remarkable ability of TNF, especially in combination with Interferon-gamma or melphalan, to inhibit the growth of malignant tumor cells is so far unmatched. Unfortunately, its high systemic toxicity and hepatotoxicity prevent its systemic use in cancer patients. An elegant manner to circumvent this problem is the isolated limb and liver perfusion for the treatment of melanoma, soft tissue sarcoma and liver tumors, respectively, although the latter method can lead to a reversible hepatotoxicity. In order to allow also the treatment of other cancers with TNF, new strategies have to be developed that aim at sensitizing tumor cells to TNF and at reducing its systemic and liver toxicity, without losing its antitumor efficiency. Moreover, the lectin-like domain of TNF, which is spatially distinct from the receptor binding sites, could be useful in reducing cancer treatment-related pulmonary edema formation. This review will discuss some recent developments in these areas, which can lead to a renewed interest in TNF for the systemic treatment of cancer.
肿瘤坏死因子（TNF）具有显著的能力，尤其是与γ干扰素或美法仑联合使用时，能够抑制恶性肿瘤细胞的生长，这一点至今仍无与伦比。不幸的是，其高度的全身毒性和肝毒性阻碍了它在癌症患者中的全身应用。一种巧妙的解决这个问题的方法是分别采用离体肢体灌注和肝脏灌注来治疗黑色素瘤、软组织肉瘤和肝脏肿瘤，尽管后一种方法可能会导致可逆性肝毒性。为了也能用TNF治疗其他癌症，必须开发新的策略，旨在使肿瘤细胞对TNF敏感，并降低其全身毒性和肝毒性，同时又不丧失其抗肿瘤效力。此外，TNF的凝集素样结构域在空间上与受体结合位点不同，可能有助于减少癌症治疗相关的肺水肿形成。本综述将讨论这些领域的一些最新进展，这些进展可能会重新引发人们对TNF用于癌症全身治疗的兴趣。
