Blocking Growth Hormone Receptor Shows Promise in Combating Treatment-Resistant Lung Cancer
Lung cancer remains the leading cause of cancer-related deaths globally, but a new study from Ohio University suggests a potential new avenue for treatment, particularly for patients who have developed resistance to existing therapies. Researchers have identified the growth hormone receptor (GHR) as a key player in cancer cell growth and treatment resistance and found that blocking this receptor may improve the effectiveness of chemotherapy.
The Role of Growth Hormone in Lung Cancer
Non-Small Cell Lung Cancer (NSCLC), the most common type of lung cancer, accounts for 80–85% of all cases. While treatments like surgery, chemotherapy, radiation, and targeted therapies have advanced, many patients eventually develop resistance, leading to poorer outcomes. The Ohio University research team investigated the role of growth hormone (GH) in NSCLC progression.
Growth hormone is well-known for its role in regulating growth and development. It exerts its effects by binding to the growth hormone receptor (GHR) on cells. Still, previous research hinted at a potential link between GH and cancer cell growth and resistance to treatment.
Study Findings: GHR Levels and Patient Outcomes
Analyzing tumor samples from hundreds of NSCLC patients using large datasets, including information from The Cancer Genome Atlas, researchers discovered significantly higher levels of GHR in lung tumors compared to normal lung tissue. This elevated GHR expression correlated with poorer patient survival rates.
Patients with low GHR tumor levels survived an average of approximately 66 months, while those with high GHR tumor levels had an average survival of only 36–40 months. This suggests that GHR levels could potentially serve as a biomarker for prognosis in NSCLC.
How GH Impacts Chemotherapy Effectiveness
Laboratory experiments using both human and mouse lung cancer cells revealed that GH enhances cancer cell resistance to common chemotherapy drugs like doxorubicin and cisplatin. GH achieves this by increasing the activity of drug-efflux pumps – proteins that actively remove chemotherapy drugs from cancer cells, reducing their effectiveness. GH similarly triggered changes linked to tumor spread and reduced cell death, further contributing to treatment resistance.
Pegvisomant: A Potential Therapeutic Agent
The researchers tested pegvisomant, a drug that blocks the growth hormone receptor. Pegvisomant, marketed as Somavert, was originally discovered by Ohio University’s John J. Kopchick, Ph.D., in 1987 and is currently approved by the U.S. Food and Drug Administration for the treatment of acromegaly, a condition characterized by excess GH production.
The study demonstrated that pegvisomant reversed many of the harmful effects caused by GH. When combined with chemotherapy, it increased cancer cell sensitivity to treatment and allowed for lower chemotherapy doses to achieve the same level of cell kill.
Future Directions and Clinical Trials
While these findings are promising, researchers emphasize that the study was conducted using patient dataset analysis and laboratory cell models. Further research, including studies in animal models, is necessary. Previous research has shown positive results with combinations of therapy and Pegvisomant in mouse models of melanoma, pancreatic, and liver cancers. The team is now planning to test the combination in lung cancer cells in mice.
Successful results in animal studies will pave the way for clinical trials to determine the safety and efficacy of this approach in human lung cancer patients.
Study Team and Funding
The research was conducted by a team 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. The team was led by John J. Kopchick, Ph.D., and included Arshad Ahmad, along with 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.
Dr. Kopchick was awarded $2.35 million in federal funding in 2025 to acquire state-of-the-art equipment to further advance cancer research and treatment at the Ohio University Heritage College of Osteopathic Medicine.