Mechanisms of resistance to ErbB-targeted cancer therapeutics.
The ErbB receptors, such as EGFR, have been intensely pursued as targets for cancer therapeutics. However, a large percentage of patients who are initially responsive to ErbB-targeted therapies experience tumor recurrence and become refractory to therapy. In this issue of the JCI, Guix et al. demonstrate that downregulation of IGF-binding protein 3 (IGFBP-3) and -4, the negative regulators of IGF-I receptor signaling, contributes to the resistance of human squamous cell carcinomas to the EGFR inhibitor gefitinib (see the related article beginning on page 2609). Understanding the mechanisms involved in the resistance of some tumors to ErbB-targeted molecules may provide guidelines for developing more efficient therapeutic approaches.
Wang
Qiang
Q
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, and Abramson Family Cancer Research Institute, Philadelphia, Pennsylvania 19104, USA.
Greene
Mark I
MI
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D000911:Antibodies, Monoclonal; D066246:ErbB Receptors; D000077156:Gefitinib; D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D019869:Phosphatidylinositol 3-Kinases; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D017526:Receptor, IGF Type 1