Researchers at Ohio University have identified a potentially groundbreaking method to enhance treatment responses in lung cancer patients, particularly for those whose cancers resist conventional therapies. The study, published in the International Journal of Molecular Science, was led by John J. Kopchick, Ph.D., a distinguished professor and Goll-Ohio Eminent Scholar, along with his graduate student Arshad Ahmad from the Heritage College of Osteopathic Medicine.
Lung cancer, particularly Non-Small Cell Lung Cancer (NSCLC), remains the leading cause of cancer-related mortality globally. NSCLC accounts for approximately 80–85% of lung cancer cases. Despite advancements in treatment modalities such as chemotherapy, surgery, and targeted therapies, many patients develop resistance, complicating management and negatively impacting survival rates.
The research team focused on the impact of growth hormone (GH) in NSCLC. While GH is primarily known for its role in regulating growth and metabolism, previous studies suggested it might also promote cancer cell proliferation and treatment resistance. Utilizing extensive patient datasets, including information from The Cancer Genome Atlas, the researchers analyzed tumor samples from hundreds of NSCLC patients. Their findings indicated that lung tumors exhibited significantly elevated levels of the growth hormone receptor (GHR) compared to normal lung tissue.
Importantly, patients with high GHR levels had a markedly reduced survival rate—averaging only 36 to 40 months—compared to approximately 66 months for those with lower GHR levels. The implications of these findings are profound, as they suggest a link between GHR levels and patient prognosis.
In laboratory experiments involving human and mouse lung cancer cells, the team discovered that GH increased resistance to chemotherapy agents such as doxorubicin and cisplatin. GH enhanced the activity of drug-efflux pumps, which function to expel chemotherapy drugs from cancer cells. This mechanism not only contributed to tumor survival but also facilitated tumor spread and reduced cell death.
As part of their research, the team evaluated the effects of pegvisomant, a drug that blocks the growth hormone receptor. Pegvisomant, marketed under the brand name Somavert, was initially approved by the U.S. Food and Drug Administration (FDA) in 2000 for the treatment of acromegaly, a condition resulting from excess GH. The study revealed that pegvisomant successfully counteracted many adverse effects associated with GH, enhancing the sensitivity of cancer cells to chemotherapy and reducing the required dosage of these drugs.
John J. Kopchick stated, “By blocking the growth hormone receptor, we may be able to improve the effectiveness of existing treatments.” This statement underscores the potential of targeting GH signaling in developing more effective therapeutic strategies against aggressive, therapy-resistant lung cancer.
While the results are promising, the researchers emphasize that their findings stem from analyses of patient datasets and laboratory cell models. Further studies, including animal models, are planned to validate the efficacy of pegvisomant in treating lung cancer. Previous research has shown that combinations of pegvisomant with other therapies significantly improved outcomes in mouse models for melanoma, pancreatic, and liver cancers. The next step for the research team is to conduct tests on lung cancer cells within mouse models, with successful outcomes paving the way for clinical trials to assess the safety and effectiveness of this approach in human patients.
This research was conducted within Ohio University’s Institute for Molecular Medicine and the Aging, Diabetes Institute, and the Translational Biomedical Sciences Program, alongside the Departments of Biomedical Sciences and Biological Sciences. The collaborative effort also includes contributions from researchers at the Erasmus Medical Centre in the Netherlands, highlighting the global effort to combat lung cancer.
As the study progresses, the hope remains that these findings will lead to improved treatment options for lung cancer patients, ultimately aiming to enhance survival rates and quality of life.
