PMID- 16931767 OWN - NLM STAT- MEDLINE DCOM- 20070409 LR - 20221109 IS - 0163-769X (Print) IS - 0163-769X (Linking) VI - 28 IP - 1 DP - 2007 Feb TI - The role of the IGF system in cancer growth and metastasis: overview and recent insights. PG - 20-47 AB - IGF-I receptor (IGF-IR) signaling and functions are mediated through the activities of a complex molecular network of positive (e.g., type I IGF) and negative (e.g., the type II IGF receptor, IGF-IIR) effectors. Under normal physiological conditions, the balance between the expression and activities of these molecules is tightly controlled. Changes in this delicate balance (e.g., overexpression of one effector) may trigger a cascade of molecular events that can ultimately lead to malignancy. In recent years, evidence has been mounting that the IGF axis may be involved in human cancer progression and can be targeted for therapeutic intervention. Here we review old and more recent evidence on the role the IGF system in malignancy and highlight experimental and clinical studies that provide novel insights into the complex mechanisms that contribute to its oncogenic potential. Controversies arising from conflicting evidence on the relevance of IGF-IR and its ligands to human cancer are discussed. Our review highlights the importance of viewing the IGF axis as a complex multifactorial system and shows that changes in the expression levels of any one component of the axis, in a given malignancy, should be interpreted with caution and viewed in a wider context that takes into account the expression levels, state of activation, accessibility, and functionality of other interacting components. Because IGF targeting for anticancer therapy is rapidly becoming a clinical reality, an understanding of this complexity is timely because it is likely to have an impact on the design, mode of action, and clinical outcomes of newly developed drugs. FAU - Samani, Amir Abbas AU - Samani AA AD - Department of Medicine, McGill University Health Center, Royal Victoria Hospital, Room H6.25687, Pine Avenue West, Montreal, Quebec, Canada H3A 1A1. FAU - Yakar, Shoshana AU - Yakar S FAU - LeRoith, Derek AU - LeRoith D FAU - Brodt, Pnina AU - Brodt P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20060824 PL - United States TA - Endocr Rev JT - Endocrine reviews JID - 8006258 RN - 0 (Somatomedins) RN - EC 2.7.10.1 (Receptor, IGF Type 1) SB - IM MH - Animals MH - Cell Cycle MH - Cell Transformation, Neoplastic MH - Disease Progression MH - Drug Resistance, Neoplasm MH - Humans MH - Models, Biological MH - *Neoplasm Metastasis MH - Neoplasms/*pathology MH - Protein Processing, Post-Translational MH - Radiation Tolerance MH - Receptor, IGF Type 1/physiology MH - Signal Transduction MH - Somatomedins/*physiology RF - 340 EDAT- 2006/08/26 09:00 MHDA- 2007/04/10 09:00 CRDT- 2006/08/26 09:00 PHST- 2006/08/26 09:00 [pubmed] PHST- 2007/04/10 09:00 [medline] PHST- 2006/08/26 09:00 [entrez] AID - er.2006-0001 [pii] AID - 10.1210/er.2006-0001 [doi] PST - ppublish SO - Endocr Rev. 2007 Feb;28(1):20-47. doi: 10.1210/er.2006-0001. Epub 2006 Aug 24.