The chemotherapy drug cisplatin (Platinol, Platinol-AQ; Bristol-Myers Squibb) can be as hard on the kidneys as it is on cancer cells. But researchers could be closing in on a way to forestall the side effect that limits the drug's usefulness.
Cisplatin is a mainstay of chemotherapy against a variety of cancers, including lung, testicular, and ovarian tumors. The standard procedure to protect the kidneys involves giving patients plenty of intravenous fluids. But more than 25% of patients still suffer from kidney damage, which can prove fatal, spurring researchers to look for an alternative method to prevent renal injury.
Just this year, several studies have reported success with cells or animal models using compounds that range from the antioxidant resveratrol to sildenafil. And an article published in June suggests it might be possible to short-circuit cisplatin's negative effects with a drug that is in clinical trials for an unrelated condition.
Pabla and colleagues [J Clin Invest 2011 Jun 1 (Epub ahead of print)] revealed that PKCδ, a protein some cancer cells need to survive, helps orchestrate renal injury in response to cisplatin. The researchers also found that 2 PKCδ inhibitors, rottlerin and δV1-1, protected the kidneys and increased the effectiveness of cisplatin against implanted tumors in mice.
“Identifying targets that can reduce toxicity is one way to improve the efficacy of drugs,” says the paper's first author, Navjotsingh Pabla of the Georgia Health Sciences University in Augusta. He suggests that because rottlerin's specificity is a matter of debate, the better bet for reducing cisplatin's toxicity is δV1-1. KAI Pharmaceuticals has started phase II trials of δV1-1 as a treatment for heart attacks.
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