Research News

Jianjun Zhao, MD, PhD, has received a five-year, nearly $2.6 million grant from the National Cancer Institute, part of the National Institutes of Health, to investigate a new approach for treating chemotherapy-associated kidney damage.

In study results published last year, Dr. Zhao and his team found that the protein APE2 may be a viable target to help treat or prevent acute kidney injury among patients treated with the chemotherapy drug cisplatin. As many as a quarter of all cancer patients treated with cisplatin will develop the condition.

"We found that genetically knocking out APE2 in preclinical models treated with cisplatin significantly reduced cisplatin-induced acute kidney injury, suggesting that pharmacologically targeting the protein may be a viable approach to treating the condition in humans," said Dr. Zhao, assistant staff in the Department of Cancer Biology. "With this new award, we will develop small molecules that can target APE2 and test how effective they are in disrupting mechanisms of disease."

In this new phase of study, Dr. Zhao and his team will continue their earlier work to develop a reliable mouse model of chemotherapy-associated kidney damage to study disease processes and test potential therapeutics. Here, they will compare the molecular features of their model to those observed in patient samples and study how APE2 interacts with other proteins, including one called MYH9, to promote acute kidney injury.

Using their model, the researchers will also test the ability of two compounds to suppress APE2 expression. "Based on our previous research, we know that using genetic engineering technology to completely prevent APE2 expression had positive effects," said Dr. Zhao, "but now we need to find feasible ways to prevent the protein's expression or activity in patients, namely through drug development."

The researchers will test two different approaches to inhibit APE2 activity in a specific type of kidney cells. They will test whether the drug candidates can overturn kidney damage in their preclinical model of cisplatin-induced acute kidney injury, as well as if they can prevent kidney injury from occurring in preclinical lung cancer models treated with cisplatin.