New Study Identifies Potential Target Against Renal Cell Carcinoma

Investigators at Rutgers Cancer Institute of New Jersey have just published a new study in the journal Cell Reports, which suggests an entirely new way of identifying and potentially treating patients with kidney tumors. By examining the inner workings of a rare benign kidney tumor, they have discovered a novel mechanism that may prevent this type of tumor from becoming malignant.

The findings from this study may be highly significant because they suggest that inhibiting mitochondria with agents such as metformin may demonstrate anticancer activity in many different cancers.

Rutgers Cancer Institute Associate Director for Basic Science Eileen White, PhD, who is a distinguished professor of molecular biology and biochemistry, and colleagues, sequenced 11 benign human renal oncocytoma samples.  Renal oncocytoma is typically not cancerous, but may have the ability to become malignant. The samples were characterized based on chromosome loss, and the researchers designated type-1 as having no chromosome loss and type-2 as having specific chromosome loss.

The researchers report that much of the cancer genome sequencing efforts to date has been aimed at malignant tumors and identifying cancer causing mutations, and their underlying mechanisms. The Rutgers researchers did the opposite. They sought to identify what limits some tumors to benign disease. They found type-2 oncocytomas with chromosome loss may progress to a subtype of malignant kidney cancer called eosinophilic chromophobe renal cell carcinoma (ChRCC). There was no evidence that type -1 oncocytoma may progress to malignant disease. 

“Identifying mechanisms that restrict some tumors such as these to benign disease can inform novel approaches to cancer therapy,” according to the Rutgers press release.

Oncocytomas displayed disruption of key cellular activities including cell waste disposal, and collection and distribution of proteins in the cell. The investigators theorize that the genetic defects in the mitochondria activate a barrier that impairs energy production. The findings point to a whole new tumor-suppressive mechanism in which mitochondrial inhibitors, like the diabetes drug metformin, may have a cancer prevention role. 

Currently, metformin is under investigation for treating certain tumor types. The study also showed a connection between p53, and adenosine monophosphate-activated protein kinase (AMPK), and the mutations with mitochondria.