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

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Insulin Resistance and Cancer

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

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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.

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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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Authors and Affiliations

  1. Department of Medicine, McGill University, Montreal, QC, Canada, H3A 1A1

    Julia V. Burnier, Shun Li & Pnina Brodt

  2. Department of Oncology, McGill University, Montreal, QC, Canada, H3A 1A1

    Pnina Brodt

  3. Department of Surgery, Surgical Labs, Royal Victoria Hospital, McGill University, Room H6.25 687 Pine Avenue, Montreal, QC, Canada, H3A 1A1

    Pnina Brodt

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  1. Julia V. Burnier
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  2. Shun Li
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  1. Mount Sinai Hospital, Dept. Medicine, University of Toronto, Murray St. 60, Toronto, M5T 3L9, Ontario, Canada

    I. George Fantus

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Burnier, J.V., Li, S., Brodt, P. (2011). The Role of the IGF Axis in Human Malignancy: Evidence from Epidemiological Studies and Tissue Analysis. In: Fantus, I. (eds) Insulin Resistance and Cancer. Energy Balance and Cancer, vol 1. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-9911-5_10

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