Targeting the insulin-like growth factor signaling pathway: figitumumab and other novel anticancer strategies

Expert Opin Investig Drugs. 2011 Sep;20(9):1293-304. doi: 10.1517/13543784.2011.602630. Epub 2011 Jul 22.

Abstract

Introduction: There are clear preclinical data that support the involvement of the insulin-like growth factor (IGF) signaling pathway in oncogenesis and cancer progression. Such evidence has led to the design and conduct of drug development programs targeting the IGF-I receptor (IGF-IR) over the past 10 years.

Areas covered: This review details the structure and function of different members of the IGF system and related pathways, describes the rationale for targeting IGF-IR in cancer and updates the current advances in drug development. The preclinical development of figitumumab, the furthest developed mAb against IGF-IR, is examined as well as the reported data from Phase I - III clinical trials. Future prospects for this target and pathway are also discussed.

Expert opinion: While there have been both successes and failures in the development of novel targeted therapeutics targeting the IGF pathway, the evaluation of such agents should continue, with greater emphasis placed on combinatorial strategies and the development of predictive biomarkers that enhance antitumor responses through appropriate patient selection.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Humans
  • Immunoglobulins, Intravenous
  • Insulin-Like Growth Factor I / drug effects*
  • Insulin-Like Growth Factor I / physiology
  • Multiple Myeloma / drug therapy
  • Neoplasms / drug therapy
  • Neoplasms / physiopathology
  • Sarcoma / drug therapy
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Immunoglobulins, Intravenous
  • Insulin-Like Growth Factor I
  • figitumumab