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- Title
Doxorubicin cardiomyopathy via TLR-2 stimulation: potential for prevention using current anti-retroviral inhibitors such as ritonavir and nelfinavir.
- Authors
Kast, R. E.; Foley, K. F.; Focosi, D.
- Abstract
Doxorubicin remains a useful anti-cancer drug but as lifetime dose approaches 500 mg/m2 and particularly when this dose is exceeded, iatrogenic life-threatening cardiomyopathy becomes progressively more likely. This note reviews evidence indicating that doxorubicin induced cardiomyopathy is partly mediated by stimulation of Toll-like receptors (TLR) 2 and 4 which are expressed on cardiomyocytes. Indinavir, nelfinavir, ritonavir, and saquinavir are currently marketed protease inhibitors used to suppress human immunodeficiency virus. They have recently been shown to inhibit signalling at TLR 2 and 4 as well as intracellular events downstream from these receptors. It is possible that these FDA-approved anti-retroviral protease inhibitors could be used off-label to diminish likelihood of doxorubicin cardiotoxicity permitting higher doxorubicin doses. We suggest that currently marketed anti-viral protease inhibitors be investigated in animal models of doxorubicin cardiomyopathy and if such studies do indeed show protection, human studies be initiated. Copyright © 2007 John Wiley & Sons, Ltd.
- Publication
Hematological Oncology, 2007, Vol 25, Issue 2, p96
- ISSN
0278-0232
- Publication type
Article
- DOI
10.1002/hon.811