Abstract
The insulin/insulin-like growth factor (IGF) system is a major determinant in the pathogenesis and progression of colorectal cancer (CRC). Indeed, several components of this signaling network, including insulin, IGF-1, IGF-2, the IGF-binding proteins, the insulin receptor (IR), the IGF-1 receptor (IGF-1R), and IR substrate proteins 1 and 2 contribute to the transformation of normal colon epithelial cells. Moreover, the insulin/IGF system is also implicated in the development of resistance to both chemotherapeutic drugs and epidermal growth factor receptor targeted agents. The identification of hybrid receptors comprising both the IR and IGF-1R adds further complexity to this signaling network. Thus, a comprehensive understanding of the biological functions performed by each component of the insulin/IGF system is required to design successful drugs for the treatment of CRC patients.
Highlights
The insulin/insulin-like growth factor (IGF) system is a multifactorial signaling network that modulates energy metabolism, cell growth, and cancer [1].To date, two insulin receptor (IR) isoforms have been described
The insulin/IGF system plays a pivotal role in the pathogenesis, progression, and prognosis of colorectal cancer (CRC)
Solid epidemiological and biological evidence indicates that hyperactivation of the insulin/IR pathway represents an early step in colon cancerogenesis, establishing both mitogenic and proangiogenic signals that favor neoplastic transformation of normal colorectal epithelial cells
Summary
The insulin/insulin-like growth factor (IGF) system is a multifactorial signaling network that modulates energy metabolism, cell growth, and cancer [1].To date, two insulin receptor (IR) isoforms have been described. It has been demonstrated that the increased blood levels of insulin in type II diabetes individuals, caused by insulin-resistance, enhance the risk to develop colon cancer [12]. Initial interest for a possible role of IGF-1 in colon cancer development stemmed from observations reporting an increased CRC incidence in patients with acromegaly, a condition characterized by elevated levels of both GH and IGF-1 [22, 23].
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