Curtailing side effects in chemotherapy: a tale of PKCδ in cisplatin treatment

Navjotsingh Pabla 1,2 , Zheng Dong 1 1 Department of Cellular Biology and Anatomy, Medical College of Georgia, Georgia Health Sciences University and Charlie Norwood Veterans Affairs Medical Center, Augusta, GA 30912 2 Present address: Division of Biology, California Institute of Technology, Pasadena, CA 91125 Received: January 28, 2012; Accepted: January 30, 2012; Published: January 31, 2012; Keywords: cisplatin, chemotherapy, side effect, protein kinase C δ Correspondence: Zheng Dong, Ph.D., email: // // Abstract The efficacy of chemotherapy is often limited by side effects in normal tissues.  This is exemplified by cisplatin, a widely used anti-cancer drug that may induce serious toxicity in normal tissues and organs including the kidneys. Decades of research have delineated multiple signaling pathways that lead to kidney cell injury and death during cisplatin treatment.  However, the same signaling pathways may also be activated in cancer cells and be responsible for the chemotherapeutic effects of cisplatin in tumors and, as a result, blockade of these pathways is expected to reduce the side effects as well as the anti-cancer efficacy.  Thus, to effectively curtail the side effects, it is imperative to elucidate and target the cell killing mechanisms that are specific to normal (and not cancer) tissues. Our recent work identified protein kinase C δ (PKCδ) as a new and critical mediator of cisplatin-induced kidney cell injury and death. Importantly, inhibition of PKCδ enhanced the chemotherapeutic effects of cisplatin in several tumor models while alleviating the side effect in kidneys, opening a new avenue for normal tissue protection during chemotherapy.