Targeting Growth Hormone Receptor to Overcome Therapy Resistance in Non-Small Cell Lung Cancer

Area of Science:

• Oncology
• Endocrinology
• Molecular Biology

Background:

• Lung cancer (LC) is a leading cause of cancer death, with non-small cell lung cancer (NSCLC) being the most common subtype.
• Growth hormone (GH) signaling is implicated in tumor progression and therapy resistance in various cancers.
• GH receptor (GHR) expression is elevated in NSCLC, suggesting a potential role in disease aggressiveness and treatment outcomes.

Purpose of the Study:

• To investigate the impact of GH signaling on therapy resistance and tumor progression in NSCLC.
• To explore the correlation between GHR expression and patient survival and therapy refractory pathways.
• To evaluate the efficacy of GHR antagonism in overcoming chemoresistance in NSCLC.

Main Methods:

• Integrated transcriptomic analyses of NSCLC patient data.
• In vitro experiments using NSCLC cell lines treated with GH and GHR antagonists.
• Assessment of gene expression related to drug-efflux pumps (ABC transporters) and epithelial-to-mesenchymal transition (EMT).

Main Results:

• High tumoral GHR expression in NSCLC patients correlates with reduced overall survival and upregulation of therapy-refractory genes.
• GH treatment promotes chemoresistance in NSCLC cell lines by activating ABC transporters and EMT pathways.
• GHR antagonism with pegvisomant counteracted GH-induced chemoresistance and significantly improved chemotherapy efficacy in vitro.

Conclusions:

• GH signaling contributes to aggressive and therapy-resistant phenotypes in NSCLC.
• GHR antagonism represents a potential therapeutic strategy to enhance chemotherapy sensitivity in NSCLC.
• Targeting GHR warrants further investigation in preclinical and clinical settings for NSCLC treatment.