Article
Role of insulin-like growth factor-1R system in colorectal carcinogenesis.
Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, 9000 Rockville Pike, Building 10/12N226, Bethesda, MD 20892, United States.
Critical Reviews in Oncology/Hematology (impact factor:
4.41).
06/2008;
66(2):91-8.
DOI:10.1016/j.critrevonc.2007.09.003
pp.91-8
Source: PubMed
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Article: The role of the insulin-like growth factor system in colorectal cancer: review of current knowledge.
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ABSTRACT: The insulin-like growth factor system, which includes insulin-like growth factors (IGF-I and IGF-II), IGF receptors (IGF-IR and IGF-IIR) and IGF binding proteins (IGFBPs), plays an important role in epithelial growth, anti-apoptosis and mitogenesis. There is a growing body of evidence showing that IGFs control growth and proliferation of several types of cancer. This review introduces the latest information on the biology of the IGF system and its pathophysiological role in the development of colorectal cancer. The growth promoting effects of IGF-I and IGF-II on cancer cells are mediated through the IGF-IR, which is a tyrosine kinase and cancer cells with a strong tendency to metastasise have a higher expression of the IGF-IR. Most of the IGFs in circulation are bound to the IGFBPs, which regulate the bioavailability of the IGFs. All IGFBPs inhibit IGF action by high affinity binding, while some of them also potentiate the effects of IGFs. Colon cancer cells produce specific proteases that degrade the IGFBP so that the IGF will be free to act on the cancer cell in an autocrine manner. Therefore, the IGFBPs play a crucial role in the development of the cancer. The current knowledge about the link between IGFs and colon cancer is mainly based on in vitro investigations. Further in vivo study is needed to understand the exact role of the IGF system, especially its binding proteins, so that they can be manipulated for the prevention and treatment of colorectal cancer.International Journal of Colorectal Disease 06/2005; 20(3):203-20. · 2.38 Impact Factor -
Article: Insulin-like growth factors and neoplasia.
Nature reviews. Cancer 08/2004; 4(7):505-18. · 37.54 Impact Factor -
Article: Inhibition of the insulin-like growth factor receptor-1 tyrosine kinase activity as a therapeutic strategy for multiple myeloma, other hematologic malignancies, and solid tumors.
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ABSTRACT: Insulin-like growth factors and their receptor (IGF-1R) have been implicated in cancer pathophysiology. We demonstrate that IGF-1R is universally expressed in various hematologic (multiple myeloma, lymphoma, leukemia) and solid tumor (breast, prostate, lung, colon, thyroid, renal, adrenal cancer, retinoblastoma, and sarcoma) cells. Specific IGF-1R inhibition with neutralizing antibody, antagonistic peptide, or the selective kinase inhibitor NVP-ADW742 has in vitro activity against diverse tumor cell types (particularly multiple myeloma), even those resistant to conventional therapies, and triggers pleiotropic antiproliferative/proapoptotic molecular sequelae, delineated by global transcriptional and proteomic profiling. NVP-ADW742 monotherapy or its combination with cytotoxic chemotherapy had significant antitumor activity in an orthotopic xenograft MM model, providing in vivo proof of principle for therapeutic use of selective IGF-1R inhibitors in cancer.Cancer Cell 04/2004; 5(3):221-30. · 26.57 Impact Factor
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Keywords
colorectal carcinogenesis
current laboratory
epidemiologic evidence
IGF-II
insulin-like growth factor
normal homeostasis
potential anti-cancer therapy
receptors
