Blocking the Growth Hormone Receptor Makes Chemo-Resistant Lung Cancer Cells More Vulnerable

Lung cancer kills more people annually than any other cancer, and the most common form - non-small cell lung cancer (NSCLC), which accounts for 80 to 85% of all cases - frequently develops resistance to standard treatment. Chemotherapy drugs that initially work begin to fail, leaving oncologists with diminishing options. Understanding why resistance develops, and whether it can be reversed, is one of the central challenges in lung cancer research.

An Ohio University study published in the International Journal of Molecular Sciences implicates a surprising molecule: growth hormone. Best known for its role in childhood development and metabolism, growth hormone appears to activate pathways in lung tumors that make cancer cells harder to kill - and blocking those pathways with an existing FDA-approved drug may restore their vulnerability to chemotherapy.

Tumor Data From Hundreds of Patients

The research team led by John J. Kopchick and graduate student Arshad Ahmad analyzed tumor samples from The Cancer Genome Atlas, a dataset containing genomic and clinical information from hundreds of NSCLC patients. The first finding was quantitative and direct: lung tumors had substantially higher levels of growth hormone receptor (GHR) protein compared to normal lung tissue.

The clinical correlation was sharper still. Patients whose tumors had low GHR expression survived an average of 66 months. Those with high GHR expression survived only 36 to 40 months - a difference of more than two years in median survival associated with a single protein's expression level.

That correlation does not prove causation, but it established a clear biological signal worth pursuing in the laboratory.

What Growth Hormone Does to Cancer Cells

In laboratory experiments using human and mouse NSCLC cell lines, the team exposed cells to growth hormone and measured the effects on their behavior. Growth hormone increased the activity of drug-efflux pumps - proteins that actively push chemotherapy drugs out of cancer cells before they can cause damage. It also triggered molecular changes associated with tumor spread and reduced programmed cell death.

The combined effect was cells that were harder to kill. Standard doses of chemotherapy drugs, including doxorubicin and cisplatin, were less effective in GH-exposed cells than in controls.

Pegvisomant as a Reversal Agent

The team then introduced pegvisomant, an FDA-approved drug that blocks the growth hormone receptor. Kopchick developed pegvisomant in 1987, and it has been used clinically for decades to treat acromegaly, a condition of excess growth hormone that causes abnormal tissue growth. Its safety profile in humans is well established.

In the lung cancer cell experiments, pegvisomant reversed the resistance effects induced by growth hormone. Cells treated with both pegvisomant and chemotherapy showed significantly lower survival than cells treated with chemotherapy alone - and the dose of chemotherapy needed to achieve a given level of cell death dropped substantially when the GHR was blocked.

"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."

Where the Research Stands Now

These results come from analysis of existing patient datasets and from cell culture experiments. Neither approach fully replicates what happens in a living patient. The team acknowledges this directly: studies in animal models are the required next step before any human trial could be considered.

Prior work from the same group has tested GHR-blocking approaches in mouse models of melanoma, pancreatic cancer, and liver cancer, finding that combinations of standard therapy and pegvisomant produced positive outcomes. The lung cancer cell findings now justify extending those mouse studies to NSCLC. Good results in that animal work would establish the preclinical foundation needed to design a human trial assessing whether pegvisomant can make lung cancer chemotherapy more effective in patients whose tumors express high levels of GHR.

That pathway - from cell model to mouse model to human trial - typically takes years. But the existence of an FDA-approved drug with a known safety profile shortens the regulatory timeline compared to developing a new compound from scratch.