The ErbB inhibitors, gefitinib, erbstatin, and tryphostin AG825, inhibit a cell signaling process controlling the death-rate of neutrophils, immune cells, which cause damage to the lungs.
A certain class of cancer drugs, ErbB inhibitors, could be used in the future to treat chronic obstructive pulmonary disease (COPD), according to research team at the University of Sheffield.
COPD develops slowly over years, and oftentimes, patients are not aware that they have it until they are between 40 and 50 years of age, according to the study. Patients with COPD experience a wide range of adverse events, including breathlessness, coughing, and frequent chest infections.
This damage to the lungs is driven by inflammation caused by immune cells called neutrophils.
In order to promote the healing of lung cells, the study authors screened a library of 326 cancer drugs and identified a number of compounds that accelerate the death of the neutrophil cells. Specific cancer drugs were found to inhibit a cell signaling process controlling neutrophil cell death. The team also discovered that editing the genes that encode the cell signaling further decreased inflammation.
The identified drug candidates were gefitinib, erbstatin, and tryphostin AG825.
“COPD is usually treated with steroids and airway muscle relaxants which ease symptoms, but there is currently no effective treatment clinically available to counteract the damage it does to the lungs,” Lynne Prince, MD, Russell Fellow at the University of Sheffield, said in a press release.
The research demonstrates that inhibitors in these ErbB kinases could have therapeutic potential in neutrophilic inflammatory disease, according to the study authors.
"The hope of these drugs is that they can clear the damaging cells from the lungs of people living with COPD, preventing any further damage and therefore the progression of the disease for the first time,” Prince said.
The drug compounds are currently available, meaning that continued research may effectively find a lead compound to benefit patients living with COPD that are ready to use. Neutrophilic inflammation is also central to the progression of other chronic inflammatory diseases, such as rheumatoid arthritis (RA). The authors noted that the research may have the potential to impact patients with RA as well.
The study authors’ next step is to examine these drugs in patients with COPD to understand how the ErbB kinase signalling process has an effect on lung inflammation and to address potential adverse events.
Rahman A, Henry K, Herman K, et al. Inhibition of ErbB kinase signalling promotes resolution of neutrophilic inflammation. eLife 2019;8:e50990. Published October 15, 2019. DOI: 10.7554/eLife.50990. Accessed January 13, 2020.