Abstract

The insulin‐like growth factor (IGF) axis plays key roles in normal tissue growth and development as well as in the progression of several tumour types and their subsequent growth and progression to a metastatic phenotype. This review explores the role of IGF system in normal germ cell development and function in addition to examining the evidence for deregulation of IGF signalling in cancer, with particular relevance to evidence supporting a role in testicular germ cell tumours (TGCTs). Despite the clear preclinical rationale for targeting the IGF axis in cancer, there has been a lack of progress in identifying which patients may benefit from such therapy. Future employment of agents targeting the IGF pathway is expected to concentrate on their use in combination with other treatments to prevent resistance and exploit their potential as chemo‐ and radiosensitizers.

Highlights

  • The insulin and insulin-like growth factor (IGF) signalling system has been implicated in a vast array of both physiological and pathological cellular processes

  • insulin-like growth factor 1 receptor (IGF1R) signalling for correct migration to the genital ridge, and the IGF system has many roles in establishing and maintaining testicular function including steroidogenesis and maintaining pluripotency in spermatogonial stem cells

  • The IGF axis is dysregulated in many tumour types and can contribute to oncogenesis via multiple disparate mechanisms, making it an attractive therapeutic target

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Summary

REVIEW ARTICLE

Keywords: AKT, cancer, insulin-like growth factor, insulin-like growth factor 1 receptor, testicular germ cell tumour, testis cancer Received: 8-Feb-2019 Revised: 1-May-2019 Accepted: 5-May-2019 doi: 10.1111/andr.12658 IGF signalling in germ cells and testicular germ cell tumours: roles and therapeutic approaches Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, London, UK

INTRODUCTION
IGF IN GERM CELLS AND TGCT
THERAPEUTIC TARGETING OF THE IGF SYSTEM IN CANCER
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