Researchers from Ohio University have identified a promising strategy to combat treatment-resistant lung cancer. Their study, published in the International Journal of Molecular Science, suggests that blocking the growth hormone receptor could enhance the effectiveness of existing lung cancer therapies. Lung cancer remains a significant health challenge, being the leading cause of cancer-related deaths globally.
The study, spearheaded by John J. Kopchick, Ph.D., a distinguished professor and the Goll-Ohio Eminent Scholar, alongside graduate student Arshad Ahmad, reveals critical insights into the role of growth hormone (GH) in non-small cell lung cancer (NSCLC). This type accounts for approximately 80-85% of lung cancer cases, and despite advancements in treatment options like surgery, chemotherapy, and targeted therapies, many patients develop resistance, complicating their prognosis.
The research team focused on the interaction between GH and NSCLC. Known primarily for its role in regulating growth and metabolism, GH binds to a protein known as the growth hormone receptor (GHR). Previous studies indicated that GH may also promote cancer cell proliferation and treatment resistance.
By analyzing extensive patient datasets, including information from The Cancer Genome Atlas, the researchers found a notable increase in GHR levels in lung tumors compared to normal lung tissue. Patients with elevated GHR levels had significantly shorter lifespans, averaging just 36 to 40 months, compared to approximately 66 months for those with lower levels.
In laboratory experiments involving human and mouse lung cancer cells, the team discovered that GH contributed to chemotherapy resistance, particularly against drugs like doxorubicin and cisplatin. The hormone increased the activity of drug-efflux pumps, which expel chemotherapy agents from cells, and triggered changes associated with tumor metastasis while reducing cell death.
To counteract these effects, the researchers tested pegvisomant, a drug that inhibits GHR. Originally developed by Kopchick in 1987 and approved by the U.S. Food and Drug Administration for treating acromegaly, pegvisomant demonstrated significant potential in reversing GH’s detrimental effects. When combined with chemotherapy, it not only made cancer cells more sensitive but also reduced the amount of chemotherapy required to achieve cell death.
Kopchick emphasizes the significance of these findings, stating, “By blocking the growth hormone receptor, we may be able to improve the effectiveness of existing treatments.”
While the results are encouraging, researchers highlight the preliminary nature of their work, which is based on patient dataset analysis and laboratory models. Further research is necessary, including animal studies to evaluate the effects of pegvisomant on lung cancer. Previous studies have indicated that combinations of therapies with pegvisomant have shown promise in treating other cancers, such as melanoma, pancreatic, and liver cancers, in mouse models.
The team plans to extend their research to lung cancer cells in mice, with successful outcomes paving the way for subsequent clinical trials. These trials will be essential to determine the safety and effectiveness of this innovative approach for lung cancer patients.
This collaborative study involved researchers from various departments within Ohio University and included contributions from the Erasmus Medical Centre in the Netherlands. This multidisciplinary effort underscores the importance of continued exploration into novel cancer therapies to improve patient outcomes.
