title: Insulin-like growth factor-1 signaling in renal cell carcinoma.
abstract: Renal cell carcinoma (RCC) incidence is highest in highly developed countries and it is the seventh most common neoplasm diagnosed. RCC management include nephrectomy and targeted therapies. Type 1 insulin-like growth factor (IGF-1) pathway plays an important role in cell proliferation and apoptosis resistance. IGF-1 and insulin share overlapping downstream signaling pathways in normal and cancer cells. IGF-1 receptor (IGF1R) stimulation may promote malignant transformation promoting cell proliferation, dedifferentiation and inhibiting apoptosis. Clear cell renal cell carcinoma (ccRCC) patients with IGF1R overexpression have 70 % increased risk of death compared to patients who had tumors without IGF1R expression. IGF1R signaling deregulation may results in p53, WT, BRCA1, VHL loss of function. RCC cells with high expression of IGF1R are more resistant to chemotherapy than cells with low expression. Silencing of IGF1R increase the chemosensitivity of ccRCC cells and the effect is greater in VHL mutated cells. Understanding the role of IGF-1 signaling pathway in RCC may result in development of new targeted therapeutic interventions. First preclinical attempts with anti-IGF-1R monoclonal antibodies or fragment antigen-binding (Fab) fragments alone or in combination with an mTOR inhibitor were shown to inhibit in vitro growth and reduced the number of colonies formed by of RCC cells.
authors.affiliation: Department of Oncology with Laboratory of Molecular Oncology, Military Institute of Medicine, Szaserow 128, 04-141, Warsaw, Poland.|First Faculty of Medicine, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Adam F
authors.initials: AF
authors.lastname: Tracz
authors.affiliation: Department of Oncology with Laboratory of Molecular Oncology, Military Institute of Medicine, Szaserow 128, 04-141, Warsaw, Poland.
authors.forename: Cezary
authors.initials: C
authors.lastname: Szczylik
authors.affiliation: Department of Medical Oncology, IRCCS San Matteo University Hospital Foundation, Pavia, Italy.
authors.forename: Camillo
authors.initials: C
authors.lastname: Porta
authors.affiliation: Department of Oncology with Laboratory of Molecular Oncology, Military Institute of Medicine, Szaserow 128, 04-141, Warsaw, Poland. cszczylik@wim.mil.pl.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Czarnecka
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D019313:BRCA1 Protein / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000473:pathology*; D049109:Cell Proliferation; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000473:pathology*; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics; D025721:WT1 Proteins / Q000235:genetics
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; C583557:IGF1 protein, human; C000597236:IGF1R protein, human; D017451:Receptors, Somatomedin; D016159:Tumor Suppressor Protein p53; D025721:WT1 Proteins; C583751:WT1 protein, human; D007334:Insulin-Like Growth Factor I; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C546842:MTOR protein, human; D017526:Receptor, IGF Type 1; D058570:TOR Serine-Threonine Kinases; C497446:VHL protein, human
keywords: IGF-1 receptor (IGF1R); Insulin-like growth factor-1 (IGF-1); Renal cell carcinoma (RCC; ccRCC)