Targeting Growth Hormone Receptor to Overcome Therapy Resistance in Non-Small Cell Lung Cancer
Abstract
Lung cancer (LC) remains the leading cause of cancer-related death in the United States despite advances in therapy.
Growth hormone (GH) action has been implicated in tumor progression and therapy resistance across multiple cancers, but its role in LC, particularly non-small cell lung cancer (NSCLC), remains poorly defined.
In cancer cells, GH promotes chemoresistance through upregulation of drug-efflux pumps, induction of epithelial-to-mesenchymal transition (EMT), and inhibition of apoptosis.
Notably, GH receptor (GHR) expression is significantly elevated in NSCLC compared to normal lung tissue, suggesting a potential therapeutic opportunity.
In this study, we investigated the impact of GH action on therapy resistance and tumor progression using integrated transcriptomic analyses and in vitro experiments.
Analyses of transcriptomic data from NSCLC patients revealed that high tumoral GHR expression correlates with reduced overall survival, and with upregulation of genes involved in distinct therapy refractory pathways.
Our in vitro studies demonstrated that GH promotes chemoresistance in NSCLC cell lines through activation of ABC transporters and EMT pathways, whereas GHR antagonism with the GH receptor antagonist, pegvisomant, effectively counteracts these effects and improves chemotherapy efficacy significantly.
Together, our findings identify GHR signaling as a contributor to aggressive and therapy-resistant phenotypes in NSCLC in vitro and suggest that GHR antagonism may enhance chemotherapy sensitivity.
These results provide a rationale for further in vivo and mechanistic studies to evaluate the therapeutic potential of targeting GHR in NSCLC.
The Di Bella's Method: Use of Somatostatin/Octreotide analogues and/or derivatives (since 1977), Retinoids (40mg per day Beta-Carotene, 10mg per day ATRA and 10mg per day Axerophthol palmitate), Melatonin (since 1974), Vitamin D, prolactin inhibitors Cabergoline and/or Bromocriptine with pseudo-Metronomic Chemotherapy Cyclophosphamide and/or Hydroxyurea (together with others chemical compounds) in Lung Cancer (the dosage and administration schedule must be individualised for each patient):
See also:
- Official Web Site: The Di Bella Method;
- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;
- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);
- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);
- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);
- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);
- Publication, 2019 Sep: Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes (from Di Bella's Foundation);
- Publication, 2020 Sep: Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives (from Di Bella's Foundation);
- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);
- Prolactin inhibitors in oncology - In vitro, review and in vivo publications;
The Di Bella's Method: Use of Somatostatin/Octreotide analogues and/or derivatives since 1977, prolactin inhibitors Cabergoline and/or Bromocriptine associated with pseudo-Metronomic Chemotherapy Cyclophosphamide and/or Hydroxyurea - together with others chemical compounds: the dosage and administration schedule must be individualised for each patient - in several Oncological Pathologies:
- Pleural Mesothelioma: clinical records on 11 patients treated with Di Bella's Method;
- Malignant pleural mesothelioma, stage T3-T4. Consideration of a case study;
- Neuroblastoma: Complete objective response to biological treatment;
- Large B-cells Non-Hodgkin's Lymphoma, Stage IV-AE: a Case Report;
- Non-Hodgkin's Lymphoma, Stage III-B-E: a Case Report;
- Oesophageal squamocellular carcinoma: a complete and objective response;
- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;
- Disease Control after Androgen Deprivation Therapy Combined with Di Bella Multitherapy;
- Complete objective response to biological therapy of plurifocal breast carcinoma;