Repurposed Cancer Drug Shows Potential in Kidney Disease

Drug found to slow cyst growth in patients with autosomal dominant polycystic kidney disease.

An anti-cancer drug may inhibit the growth of cysts in patients with autosomal dominant polycystic kidney disease (ADPKD), new findings suggest.

ADPKD is an inherited disorder in which cysts grow in the kidney, causing it to enlarge. Patients gradually lose kidney function and often develop kidney failure.

The mutations that cause the disease affect a protein involved in various signaling pathways that often involve tyrosine kinases enzymes.

Based on this knowledge, investigators sought to examine the effects of the cancer drug bosutinib (Bosulif), which targets Src/Bcr-Abl. Bosutinib is a tyrosine kinase inhibitor approved to treat adults with Philadelphia chromosome-positive chronic myelogenous leukemia.

Included in the phase 2 study were 172 patients with ADPKD who were randomized 1:1:1 to receive either 200 mg of bosutinib daily, 400 mg of bosutinib daily, or placebo. Of the participants, 169 received at least 1 treatment; however, the higher dose of bosutinib was not well tolerated.

The results of the study, published in the Journal of the American Society of Nephrology, showed the annual rate of kidney enlargement was reduced by 66% for patients in the 200-mg arm compared with the placebo arm.

For all patients who received bosutinib, kidney enlargement was reduced by 82% compared with placebo.

There was no evidence of a benefit associated with bosutinib compared with placebo on kidney function; however, the study was not designed to demonstrate a treatment effect on kidney function.

“The reduction in growth of cysts through treatment with bosutinib was confirmed, although gastrointestinal side effects (primarily diarrhea), which were partly dose-dependent, may represent a substantial drawback for the further development of the drug for patients with ADPKD,” said lead investigator Vladimir Tesar, MD, PhD.