Researchers at Ohio University have identified a potential new approach to treating lung cancer that is resistant to current therapies. The study, led by John J. Kopchick, Ph.D., and graduate student Arshad Ahmad at the Heritage College of Osteopathic Medicine, was published in the International Journal of Molecular Science.
Lung cancer is the leading cause of cancer-related deaths both in the United States and globally. Non-Small Cell Lung Cancer (NSCLC) accounts for about 80–85% of all cases. Although there have been advances in surgery, chemotherapy, radiation, and targeted therapies, many patients develop resistance to treatment over time.
The research focused on the role of growth hormone (GH) in NSCLC. GH is primarily known for its role in regulating height and metabolism by binding to the growth hormone receptor (GHR). Previous studies have suggested that GH may also contribute to cancer cell growth and resistance to therapy.
By analyzing large datasets from sources such as The Cancer Genome Atlas, the team found that NSCLC tumors had much higher levels of GHR compared to normal lung tissue. Patients with high GHR expression in their tumors had significantly shorter survival times—an average of 36–40 months—compared to about 66 months for those with low GHR expression.
Laboratory experiments using human and mouse lung cancer cells showed that GH made these cells more resistant to common chemotherapy drugs like doxorubicin and cisplatin. This increased resistance was linked to greater activity of drug-efflux pumps that remove chemotherapy agents from cancer cells, as well as changes associated with tumor spread and reduced cell death.
The researchers then tested pegvisomant, a drug that blocks the growth hormone receptor and is approved by the U.S. Food and Drug Administration for treating acromegaly. Pegvisomant was discovered by Kopchick in 1987. In laboratory studies, pegvisomant reversed many negative effects caused by GH when combined with chemotherapy, making cancer cells more sensitive to treatment and allowing lower doses of chemotherapy drugs to be effective.
While these results are encouraging, the researchers note that their work so far has involved patient data analysis and laboratory cell models. Additional research will include testing lung cancer treatments with pegvisomant in mice. Previous studies using combinations of therapy and pegvisomant have shown positive results against melanoma, pancreatic, and liver cancers in mouse models. If similar outcomes are observed in lung cancer models, this could lead to clinical trials aimed at determining safety and effectiveness for patients.
The study involved scientists from several departments at Ohio University as well as Sebastian J.C.M.M. Neggers from Erasmus Medical Centre in the Netherlands.
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