Tumor necrosis factor and chemotherapeutic drugs targeted at DNA topoisomerase II for the treatment of genitourinary malignancies.
Recombinant TNF as a single agent for human cancer appears to be of limited value. However, rTNF has synergistic anticancer effects when combined with chemotherapeutic drugs targeted at DNA topoisomerase II. This effect of rTNF has been observed in several in vitro and in vivo tumor models, both in animal and human studies. The mechanism of this interaction appears to involve lesions to the DNA of tumor cells mediated by inhibition of DNA topoisomerase II. The combinations of rTNF plus doxorubicin and rTNF plus etoposide administered systemically are currently under evaluation by clinical trials in patients with advanced cancers. Determination of the efficacy of such combination therapy must await the completion of phase I and II trails. Other routes of administration that might increase the local concentration of rTNF and could be combined with topoisomerase II-targeted drugs include intravesical administration and the use of tumor-infiltrating lymphocytes.
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Alexander
D000818:Animals; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004317:Doxorubicin / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005047:Etoposide / Q000008:administration & dosage*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*; D014565:Urogenital Neoplasms / Q000628:therapy*
D014409:Tumor Necrosis Factor-alpha; D005047:Etoposide; D004317:Doxorubicin; D004250:DNA Topoisomerases, Type II