Vasculature-targeted tumor necrosis factor-alpha increases the therapeutic index of doxorubicin against prostate cancer
Version of Record online: 24 APR 2008
Copyright © 2008 Wiley-Liss, Inc.
Volume 68, Issue 10, pages 1105–1115, 1 July 2008
How to Cite
Bertilaccio, M. T.S., Grioni, M., Sutherland, B. W., Degl'Innocenti, E., Freschi, M., Jachetti, E., Greenberg, N. M., Corti, A. and Bellone, M. (2008), Vasculature-targeted tumor necrosis factor-alpha increases the therapeutic index of doxorubicin against prostate cancer. Prostate, 68: 1105–1115. doi: 10.1002/pros.20775
- Issue online: 23 MAY 2008
- Version of Record online: 24 APR 2008
- Manuscript Accepted: 17 MAR 2008
- Manuscript Received: 21 NOV 2007
- Associazione Italiana per la Ricerca sul Cancro. Grant Numbers: 58/2003, 2005-2007
- Ministero dell'Università e della Ricerca. Grant Number: FIRB-RBIP06LCA9-005
- mouse model;
Poor penetration and uneven distribution of doxorubicin in tumors limits the efficacy of this drug in patients with prostate cancer (PC). Aim of the study was to investigate whether pre-treatment with NGR-TNF, a tumor necrosis factor-α derivative able to target tumor vessels and alter vessel permeability, increases the penetration and the efficacy of doxorubicin in pre-clinical models of PC.
Wild type C57BL/6 mice bearing androgen-independent TRAMP-C1 PC and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, which spontaneously develop PC and metastasis, were treated with repeated cycles of doxorubicin, administered either alone or following NGR-TNF. Tumor growth and drug uptake by cancer cells was evaluated.
Doxorubicin as a single agent blocked the growth of TRAMP-C1 cells in vitro but not in vivo. Pre-treatment of mice bearing subcutaneous TRAMP-C1 tumors with NGR-TNF favored doxorubicin penetration into the tumor mass, and in both TRAMP-C1 and TRAMP models significantly delayed tumor growth without increasing drug-related toxicity.
Pre-treatment with NGR-TNF significantly expanded the therapeutic index of doxorubicin in mouse models of hormone-dependent and -independent PC. Prostate 68:1105–1115, 2008. © 2008 Wiley-Liss, Inc.