Cancer Therapy Could Be Used Against Pulmonary Fibrosis, Study Suggests
Researchers discovered a molecule that promotes lung fibrosis by integrating large amounts of data from patients, cell experiments, and animal models.
They also used a big data approach to identify a potential treatment that targets the factor — a cancer therapy that is already in clinical trials.
The study, “Hsp90 regulation of fibroblast activation in pulmonary fibrosis,” showed that the drug prevented fibrosis progression in mice. The report was published in the journal JCI Insight.
Since the treatment is already in clinical trials for various cancers, researchers at Cincinnati Children’s Hospital Medical Center believe the road to testing the compound in pulmonary fibrosis patients will be relatively short. But more studies are needed before a clinical trial can be started, they cautioned.
“We investigated how fibroblasts become dysregulated, leading to their persistent activation and fibrosis,” Anil Goud Jegga, DVM, one of the study’s two senior investigators, said in a press release. “We found that Hsp90 activity is elevated in fibroblasts isolated from fibrotic lesions and that it serves to activate the development of pulmonary fibrosis. By understanding this molecular mechanism, we were able to identify and test a potential treatment to reverse established and ongoing fibrotic lung disease.”
The research team homed in on Hsp90, or heat shock protein 90. They singled it out by comparing data on gene activity in patient tissue samples with data on gene activity in experiments involving compounds that disrupt intracellular processes. The protein exists in fibroblasts, a cell type in connective tissue that plays a key role in fibrosis development.
Fortunately, Hsp90 is no stranger to researchers: Several blockers of the factor exist. Further experiments showed that one inhibitor, 17-AAG, slowed progression of lung fibrosis in a mouse model of the condition.
“Our study also provides preclinical data to test safety and efficacy of 17-AAG or other Hsp90 inhibitors as potential treatment in patients with severe fibrotic lung disease,” said Satish K. Madala, PhD., the study’s second senior investigator.
“The small molecule Hsp90 inhibitors are currently in advanced clinical trials for various cancers. Hence, findings of this study can be relatively rapidly translated into clinical trials in patients with fibrotic diseases,” Mandala said.