The Role of the IGF Axis in Human Malignancy: Evidence from Epidemiological Studies and Tissue Analysis

Chapter
Part of the Energy Balance and Cancer book series (EBAC, volume 1)

Abstract

Clinical and experimental evidence obtained over the last three decades has collectively identified the insulin-like growth factor (IGF) axis as a major player in human cancer progression. This has led to a concerted effort to target the IGF axis, particularly the IGF-I receptor, for cancer therapy and has already resulted in the development of several inhibitors including insulin-like growth factor-I receptor (IGF-IR) antibodies and specific kinase inhibitors that have advanced into the clinic, with promising results. Detailed reviews on the role of the IGF-IR in malignancy based on animal studies and clinical evidence and on current therapeutic strategies for targeting the IGF axis are provided by other chapters in this collection. In this chapter, we review the epidemiological studies that have contributed to the identification of circulating IGF levels as a potential cancer risk factor and discuss possible reasons for, and the implications of, the disparity in the results obtained in different clinical studies. In addition, recent evidence, based on gene and protein arrays, that identifies IGF axis proteins as potential molecular regulators of tumor invasion is also reviewed highlighting the potential functional relevance of circulating and tumor-derived IGFs to cancer progression and metastasis.

Keywords

Obesity Migration Estrogen Adenoma Testosterone 

Abbreviations

ALS

Acid-labile subunit

CRC

Colorectal carcinoma

ECM

Extracellular matrix

ELISA

Enzyme-linked immunosorbent assay

GH

Growth hormone

GI

Gastrointestinal

HCC

Hepatocellular carcinoma

HGF

Hepatocyte growth factor

HNSCC

Head and neck squamous cell carcinoma

HPV

Human papilloma virus

IGF

Insulin-like growth factor

IGFBP

Insulin-like growth factor binding protein

IGFIR

Insulin-like growth factor-I receptor

IHC

Immunohistochemistry

IR

Insulin receptor

IRMA

Immunoradiometric assay

MCF

Human breast adenocarcinoma cell line

MMP

Matrix metalloproteinase

MT1-MMP

Membrane type 1 matrix metalloproteinase

NSCLC

Non–small-cell lung cancer

PDGF

Platelet-derived growth factor

PIN

Prostatic intraepithelial neoplasia

PSA

Prostate specific antigen

RIA

Radioimmunoassay

SCLC

Small-cell lung cancer

SIL

Squamous intraepithelial lesion

uPA

Urokinase plasminogen activator

uPAR

uPA receptor

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of MedicineMcGill UniversityMontrealCanada
  2. 2.Department of OncologyMcGill UniversityMontrealCanada
  3. 3.Department of Surgery, Surgical Labs, Royal Victoria HospitalMcGill UniversityMontrealCanada

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