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The insulin receptor/insulin-like growth factor receptor family as a therapeutic target in oncology

Michael Pollak1

  • 1Department of Oncology, McGill University, Jewish General Hospital, Montreal, Quebec, Canada. michael.pollak@mcgill.ca

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|January 5, 2012
PubMed

Insights

Drug candidates targeting the insulin receptor/insulin-like growth factor (IGF) receptor family showed disappointing Phase III results in cancer patients. Future trials need optimized designs based on new insights, not repeated past approaches.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The insulin receptor/insulin-like growth factor (IGF) receptor family is implicated in cancer development.
  • Numerous drug candidates targeting this family have been developed, including antibodies and tyrosine kinase inhibitors.

Purpose of the Study:

  • To evaluate the clinical efficacy of drug candidates targeting the insulin receptor/IGF receptor family in cancer.
  • To assess the impact of these therapies in large-scale clinical trials.

Main Methods:

  • Development and testing of over a dozen drug candidates (e.g., antibodies, tyrosine kinase inhibitors).
  • Conducting ambitious clinical trial programs, including Phase III trials for anti-IGF-I receptor antibodies.

Main Results:

  • Several recently reported Phase III trials for anti-IGF-I receptor antibodies yielded disappointing outcomes.
  • The tested antibodies did not demonstrate significant favorable impacts in unselected cancer patient populations.

Conclusions:

  • The hypothesis that tested antibodies have large favorable impacts on unselected cancer patients is disproven.
  • Future research requires optimized clinical trial designs incorporating recent pathophysiological insights and predictive biomarkers, rather than repeating previous strategies.

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