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.
Highlights
Cancer is the most devastating and intractable human disease
While our study suggested a renal protective strategy during cisplatin chemotherapy by targeting protein kinase C δ (PKCδ), we were concerned that PKCδ inhibition might attenuate the anti-cancer efficacy of cisplatin in tumors
By including normal tissue specific-protective agents in chemotherapy, these strategies may increase the therapeutic window. In line with this idea, PKCδ has been demonstrated to be a critical component in nephrotoxicity during cisplatin treatment
Summary
Received: January 28, 2012, Accepted: January 30, 2012, Published: January 31, 2012 Copyright: © Pabla et al This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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