Acute Kidney Injury-Induced Systemic Inflammation and Risk of Kidney Cancer Formation

In this issue of Cancer Research, Zhou and colleagues investigate the role of acute kidney injury (AKI) and AKI-associated systemic inflammation in the development of kidney cancer. They demonstrate a positive association between the formation of clear-cell renal cell carcinoma and AKI induced by ischemia-reperfusion injury in genetically modified mice. In parallel with the emergence of kidney tumors, mice with ischemic injury develop systemic inflammation associated with tissue infiltration by neutrophils and fibroblasts and upregulated expression of several inflammatory factors, with CXCL1 displaying the highest levels of upregulation. Accordingly, blockade of CXCL1-mediated signaling inhibited the emergence of kidney tumors in mice subjected to ischemic kidney injury. The study provides evidence for a new experimental approach to prevent the formation of clear-cell renal cell carcinoma and reduce kidney cancer incidence through modulation of the AKI-induced inflammatory response using inhibitors of CXC/CXCR2 axis. As the incidence of kidney cancer continues to increase, new treatment strategies for this devastating disease are urgently needed. Zhou and colleagues provide preclinical proof of concept for a new therapeutic strategy and address an unmet need for this difficult to prevent and treat cancer disease.See related article by Zhou et al., p. 2690.