Cisplatin is one of the most widely used anticancer chemotherapeutics. However, it has some severe side effects in normal tissues, in particular it is toxic to the kidneys. Understanding the mechanisms underlying this toxicity could identify targets for drugs that could be given together with cisplatin to protect the kidney during chemotherapy. In this context, a team of researchers, led by Zheng Dong, at Georgia Health Sciences University, Augusta, has now identified the signaling protein PKC-delta as a critical regulator of cisplatin-mediated kidney toxicity in mice. Importantly, inhibiting PKC-delta not only protected the kidneys from the toxic effects of cisplatin but also enhanced the antitumor effects of the drug in several xenograft and syngeneic mouse tumor models. The team therefore suggests that targeting PKC-delta could help reduce the severe kidney toxicity that occurs in cancer patients undergoing chemotherapy with cisplatin and other cisplatin-based chemotherapeutics.
TITLE: Inhibition of PKC-delta reduces cisplatin-induced nephrotoxicity without blocking chemotherapeutic efficacy in mouse models of cancer
AUTHOR CONTACT:
Zheng Dong
Medical College of Georgia and Charlie Norwood VA Medical Center, Augusta, Georgia, USA.
Phone: 706.721.2825; Fax: 706.721.6120; E-mail: zdong@mail.mcg.edu .
View this article at: http://www.jci.org/articles/view/45586?key=93f34735232ae0bf2ab0
Journal of Clinical Investigation