Antitumor effects of hormone-releasing hormone growth (GHRH) antagonists, in combination with chemotherapy drugs, in the treatment of malignant pleural mesothelioma.
1Department of Medical Sciences, University of Turin; 2Division of Endocrinology, Diabetes and Metabolism, Department of Medicine Miller School of Medicine, University of Miami, Miami, FL; 3Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, Miami, FL
Malignant pleural mesothelioma (MPM) is an aggressive tumor associated with exposure to asbestos, for which the prognosis is unfavorable and the treatments are ineffective. The effects of growth hormone-releasing hormone (GHRH) antagonists, a hormone that stimulates the release of the growth hormone (GH), have been demonstrated in many papers, with regard to their ability to inhibit the growth of numerous types of tumor, in in vitro and in vivo experimental models, such as prostate, breast and lung cancer.
Our research group has recently demonstrated the ability of latest-generation GHRH antagonists, MIA-602 and MIA-690, to reduce the survival and growth of human MPM cells in culture, derived from patients, and to inhibit the growth of this tumor in in vivo animal experimental models.
These results suggested a potential therapeutic role for GHRH antagonists in the treatment of MPM.
Therefore, the aim of this new paper is to evaluate the effect of MIA-690, the most effective of the antagonists tested so far, in combination with the chemotherapies currently used in the therapy of MPM, pemetrexed and cisplatin, in in vitro and in vivo human cell models of MPM.
The aim of this study is to demonstrate that GHRH antagonists can act in combination with chemotherapeutic substances by enhancing their anti-tumor effects, thus allowing not only to increase their efficacy, but also to reduce the toxic effects associated with chemotherapy.
From the results of this study, we hope to observe the positive interaction between GHRH antagonists and pemetrexed/cisplatin, in order to identify, at a later stage, a potential effective treatment for this disease through the development of further preclinical studies and clinical studies in humans.