Peptide hormones and lung cancer.
Several peptide hormones have been identified which alter the proliferation of lung cancer. Small cell lung cancer (SCLC), which is a neuroendocrine cancer, produces and secretes gastrin releasing peptide (GRP), neurotensin (NT) and adrenomedullin (AM) as autocrine growth factors. GRP, NT and AM bind to G-protein coupled receptors causing phosphatidylinositol turnover or elevated cAMP in SCLC cells. Addition of GRP, NT or AM to SCLC cells causes altered expression of nuclear oncogenes, such as c-fos, and stimulation of growth. Antagonists have been developed for GRP, NT and AM receptors which function as cytostatic agents and inhibit SCLC growth. Growth factor antagonists, such as the NT1 receptor antagonist SR48692, facilitate the ability of chemotherapeutic drugs to kill lung cancer cells. It remains to be determined if GRP, NT and AM receptors will served as molecular targets, for development of new therapies for the treatment of SCLC patients. Non-small cell lung cancer (NSCLC) cells also have a high density of GRP, NT, AM and epidermal growth factor (EGF) receptors. Several NSCLC patients with EGF receptor mutations respond to gefitinib, a tyrosine kinase inhibitor. Gefitinib relieves NSCLC symptoms, maintaining stable disease in patients who are not eligible for systemic chemotherapy. It is important to develop new therapeutic approaches using translational research techniques for the treatment of lung cancer patients.
Moody
T W
TW
Department of Health and Human Services, National Cancer Institute, Center for Cancer Research, Office of the Director, Bethesda, MD 20892, USA. moodyt@mail.nih.gov
D053607:Adrenomedullin; D000595:Amino Acid Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000209:etiology / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000209:etiology / Q000378:metabolism; D019886:Gastrin-Releasing Peptide / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D008969:Molecular Sequence Data; D009496:Neurotensin / Q000235:genetics / Q000378:metabolism; D036361:Peptide Hormones / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism
D036361:Peptide Hormones; D010455:Peptides; D053607:Adrenomedullin; D009496:Neurotensin; D019886:Gastrin-Releasing Peptide