Cancer Treatments Exhibit Potential Therapeutic Efficacy Toward COPD, Study Shows

Specific cancer drugs were shown to inhibit cell signaling processes that contribute to neutrophils, immune cells that cause inflammation to the lungs and serve as the main driver of lung damage in patients with chronic obstructive pulmonary disease (COPD), according to study findings published in the journal eLife.

COPD is an incurable but treatable lung disease that affects 27 million people in the United States and is the fourth leading cause of death across the nation. Patients with COPD experience a variety of symptoms, including breathlessness, coughing, and frequent chest infections, which intensify through lung damage driven by immune cells called neutrophils. These immune cells are typically activated to promote inflammation after an injury or infection to aid the healing process, but when they fail to die by a regulated process known as apoptosis, they can cause damage to the lungs.

Enzymes known as kinases are shown to control apoptosis and other cell processes, prompting a research team at the University of Sheffield to evaluate the use of effective treatments for some types of cancer and other conditions that include specific kinase inhibitors:

• Researchers screened a library of 367 kinase-inhibiting drugs to identify 1 that promotes apoptosis in human neutrophils.
• Additional tests were completed through a zebrafish tail fin injury model to uncover common targets of compounds that accelerated inflammation resolution, as well as on mice to test the efficacy of identified kinase-inhibiting drugs promoting apoptosis in neutrophils.

After screening the kinase-inhibiting drugs, researchers found that human neutrophils treated with drugs that inhibit the ErbB family of kinases died by apoptosis more quickly than untreated neutrophils, indicating the potential of these drugs for patients with COPD.

In the analysis conducted on zebrafish with injured tail fins, those treated with the ErbB-inhibiting cancer drug known as Tyrphostin AG825 had lower levels of inflammation and their neutrophils underwent apoptosis more frequently than untreated zebrafish. Furthermore, reducing the activity of 2 genes that encode ErbB kinases in zebrafish through gene editing revealed a decrease in the levels of inflammation in the model.

Tests on mice confirmed results from the prior 2 experiments, as neutrophils in the lungs of mice treated with Tyrphostin AG825 underwent apoptosis more frequently than those in untreated mice, with dead neutrophils being effectively cleared by other immune cells called macrophages that assist in limiting damage caused by neutrophils.

Study author Lynne Prince, MD, MSc, PhD, Russel Fellow at the University of Sheffield, stressed the lack of an effective treatment clinically available to counteract the damage caused to lungs by COPD, as current therapies involve steroids and airway muscle relaxants. Focusing on ErbB kinases could prove to be a potential therapeutic breakthrough in neutrophilic inflammatory disease, based on study findings.

“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,” said Prince in a press release.

Prince noted that next steps involve finding potential ways to test these drugs in people with COPD to understand how the ErbB kinase signaling process has an effect on lung inflammation and to address any adverse effects that may occur.

Reference

Rahman A, Henry KM, Herman KD, et al. Inhibition of ErbB kinase signalling promotes resolution of neutrophilic inflammation [published online October 15, 2019]. eLife. doi: 10.7554/eLife.50990.001.