Curtailing side effects in chemotherapy: a tale of PKCδ in cisplatin treatment
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.Citation
Oncotarget. 2012 Jan 31; 3(1):107-111Related articles
- Inhibition of PKCδ reduces cisplatin-induced nephrotoxicity without blocking chemotherapeutic efficacy in mouse models of cancer.
- Authors: Pabla N, Dong G, Jiang M, Huang S, Kumar MV, Messing RO, Dong Z
- Issue date: 2011 Jul
- Protein Kinase C<i>δ</i> Suppresses Autophagy to Induce Kidney Cell Apoptosis in Cisplatin Nephrotoxicity.
- Authors: Zhang D, Pan J, Xiang X, Liu Y, Dong G, Livingston MJ, Chen JK, Yin XM, Dong Z
- Issue date: 2017 Apr
- PRKCD/PKCδ contributes to nephrotoxicity during cisplatin chemotherapy by suppressing autophagy.
- Authors: Zhang D, Xu X, Dong Z
- Issue date: 2017 Mar 4
- Cisplatin nephrotoxicity: mechanisms and renoprotective strategies.
- Authors: Pabla N, Dong Z
- Issue date: 2008 May
- G31P, CXCR1/2 inhibitor, with cisplatin inhibits the growth of mice hepatocellular carcinoma and mitigates high‑dose cisplatin-induced nephrotoxicity.
- Authors: Li L, Khan MN, Li Q, Chen X, Wei J, Wang B, Cheng JW, Gordon JR, Li F
- Issue date: 2015 Feb