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Deciphering the role of insulin-like growth factor-I receptor in trastuzumab resistance

Rita Nahta1

  • 1Departments of Pharmacology, Hematology and Medical Oncology, School of Medicine; Winship Cancer Institute; Molecular and Systems Pharmacology Program, Graduate Division of Biological and Biomedical Sciences, Emory University, Suite 5001, 1510 Clifton Road, Atlanta, GA 30322, USA.

Chemotherapy Research and Practice
|July 26, 2012
PubMed

Insights

Insulin-like growth factor-I receptor (IGF-IR) signaling drives resistance to HER2-targeted trastuzumab in breast cancer. Inhibiting IGF-IR may restore sensitivity to trastuzumab and overcome treatment resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Trastuzumab is a HER2-targeted therapy for HER2-overexpressing metastatic breast cancer.
  • Resistance to trastuzumab is a significant clinical challenge.
  • Increased insulin-like growth factor-I receptor (IGF-IR) signaling is implicated in trastuzumab resistance.

Purpose of the Study:

  • To review the role of IGF-IR signaling in trastuzumab resistance.
  • To explore cotargeting IGF-IR and HER2 as a therapeutic strategy.

Main Methods:

  • Literature review and synthesis of preclinical and clinical data.
  • Discussion of genetic and pharmacologic inhibition of IGF-IR signaling.
  • Analysis of therapeutic strategies for trastuzumab-resistant breast cancer.

Main Results:

  • IGF-IR signaling is a key mechanism contributing to trastuzumab resistance.
  • Inhibition of IGF-IR signaling can re-sensitize breast cancer cells to trastuzumab.
  • Cotargeting IGF-IR and HER2 shows promise for overcoming resistance.

Conclusions:

  • IGF-IR plays a critical role in mediating resistance to HER2-targeted therapy.
  • Targeting IGF-IR, in combination with HER2-targeted agents, represents a viable therapeutic approach.
  • Further investigation into cotargeting strategies is warranted for HER2-overexpressing breast cancers.

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