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The Role of ErbB Inhibitors in Trastuzumab Resistance

Indiana University School of Medicine, Indianapolis, Indiana, USA

Correspondence: Kathy D. Miller, M.D., Indiana University School of Medicine, Indiana Cancer Pavilion, 535 Barnhill Drive, RT-473, Indianapolis, Indiana 46202, USA. Telephone: 317-274-0920; Fax: 317-274-3646; e-mail: kathmill{at}iupui.edu

The ErbB family of receptors and ligands is a complex, delicately balanced system involved in the growth and differentiation of normal human cells as well as neoplasms. Targeting this system with therapies that inhibit ErbB receptor activity in cancer patients has been somewhat successful, but resistance to ErbB inhibitor monotherapy is substantial. An understanding of the biology of ErbB receptor inhibitors is necessary to determine how best to utilize them in treatment regimens. Experimental evidence has provided valuable insights regarding mechanisms involved in resistance, and indicates that resistance can be reversed in some models. Ongoing studies in patients are evaluating whether agents that target both the epidermal growth factor (EGFR, ErbB-1) and ErbB-2 (HER-2) receptors can prevent or delay resistance in patients with metastatic breast cancer that overexpresses HER-2. With a better understanding of the biology of breast cancer, and with several novel ErbB receptor inhibitors in development, continued progress for improved patient outcomes is expected.

Key Words. Breast cancer • Resistance • Trastuzumab • Tyrosine kinase receptor

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