The role of insulin-like growth factor system in soft tissue sarcomas: from physiopathology to targeted therapeutic approaches.
Purpose/Results. Although surgical, chemo- and radiotherapeutic treatment regimens in patients with soft tissue sarcomas have constantly been refined over the past two decades, the survival rate for these patients is rather low.Discussion. There is a great need to investigate the mechanisms for oncogenesis and to identify the factors involved in malignant transformation in sarcomas. Among these factors, IGFs are thought to play a pivotal role as progression factors in various types of sarcomas. The dysregulation of the IGF-II synthesis, e.g. by loss of imprinting which occurs in most types of sarcomas, is a permissive effect through the suppression of cell death. In addition, cells that overexpress the type I IGF receptors are more susceptible to transformation by oncogenes. As TP53 suppresses the activity of IGF-II P3 and P4, as well as the type I IGF receptor promoter, mutations of TP53 in sarcomas may alternatively lead to the activation of these factors. Finally, the phenomenon of non-islet cell tumour hypoglycaemia that occurs in patients with sarcomas, and which is related to the secretion of IGF-II prohormones, is discussed. Future therapeutic strategies may be based upon the application of antibodies or antisense oligonucleotides directed against the type I IGF receptors, with the common goal of inducing apoptosis in sarcoma cells. Ultimately, these and other therapeutic approaches may lead to a better outcome in patients suffering from sarcoma.
Zumkeller
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Department of Hematology/Oncology Children's University Hospital Heidelberg Germany.