New study identifies growth hormone receptor as possible target to improve lung cancer treatment

Researchers at Ohio University have discovered what may be a new way to fight lung cancer that is resistant to other treatments. The study, led by Goll-Ohio Eminent Scholar and distinguished professor John J. Kopchick, Ph.D., and his graduate student Arshad Ahmad at the Heritage College of Osteopathic Medicine, found that blocking the growth hormone receptor may help make lung cancer treatments more effective.

Lung cancer remains the leading cause of cancer-related deaths in the United States and worldwide. The most common type, Non-Small Cell Lung Cancer (NSCLC), makes up about 80–85% of all lung cancer cases. Although surgery, chemotherapy, radiation and targeted therapies have improved over time, many patients develop resistance to treatment. This makes the disease harder to control and lowers survival rates.

The research team studied the role of growth hormone (GH) in NSCLC. Growth hormone is best known for helping regulate height, metabolism and body development. It works by binding to a protein in cells called the growth hormone receptor (GHR). However, previous research has suggested that GH may also help cancer cells grow and resist treatment.

Using large patient datasets, including information from The Cancer Genome Atlas, the researchers analyzed tumor samples from hundreds of NSCLC patients. They found that lung tumors had much higher levels of the GHR compared to normal lung tissue. Importantly, patients whose tumors had high levels of GHR lived significantly shorter lives than those with low levels. On average, patients with low GHR tumors survived about 66 months, while those with high GHR tumors survived only 36–40 months.

In laboratory experiments using human and mouse lung cancer cells, the team found that GH made cancer cells more resistant to chemotherapy drugs such as doxorubicin and cisplatin. GH increased the activity of special proteins known as drug-efflux pumps, which push chemotherapy drugs out of cancer cells. It also triggered changes linked to tumor spread and reduced cell death. Together, these effects made the cancer cells tougher and harder to kill.

The researchers then tested the drug, pegvisomant, which blocks the growth hormone receptor. Pegvisomant, sold under the brand name Somavert, was discovered by Kopchick in 1987 and is approved by the U.S. Food and Drug Administration to treat acromegaly, a condition caused by excess GH. In the recently published studies, Kopchick’s research team noted that pegvisomant reversed many of the harmful effects caused by GH. When combined with chemotherapy, it made cancer cells much more sensitive to treatment and lowered the dose of chemotherapy needed to kill the cells.

“These findings suggest that growth hormone signaling helps drive aggressive and therapy-resistant lung cancer,” said Kopchick. “By blocking the growth hormone receptor, we may be able to improve the effectiveness of existing treatments.”

While the results are promising, the researchers caution that the study was performed using patient dataset analysis and laboratory cell models. More research, including studies in animals has shown that combinations of therapy and Pegvisomant significantly and positively treated melanoma, pancreatic, and liver cancers in mouse models. Now the team will test lung cancer cells in mice. Good results will lay the foundation for subsequent clinical trials, which are required to determine whether this approach is safe and effective for lung cancer patients.

This study was conducted by researchers at Ohio University’s Institute for Molecular Medicine and the Aging, the Diabetes Institute, the Translational Biomedical Sciences Program, and the Departments of Biomedical Sciences and Biological Sciences at Ohio University. Along with Kopchick and Arshad Ahmad, the research team includes Reetobrata Basu, Caden Fyffe, Reece Geiger, Christopher Walsh, Delany Minto, Edward Brenya, Amrutha Varshini Alur and Sebastian J.C.M.M. Neggers at the Erasmus Medical Centre in the Netherlands.