Trastuzumab-lnduced HER reprogramming in "Resistant" breast carcinoma cells

Murli Narayan, Jason A. Wilken, Lyndsay N. Harris, Andre T. Baron, Kimberly D. Kimbler, Nita J. Maihle

Research output: Contribution to journalArticlepeer-review

183 Scopus citations


Although trastuzumab (Herceptin) is an important advance in the treatment of breast cancer, a significant proportion of patients do not respond to trastuzumab either alone or in combination with chemotherapy. In this study, we observe that epidermal growth factor receptor (EGFR) and HER3 expression is substantially increased after long-term trastuzumab exposure of HER2-positive breast carcinoma-derived cell lines that show primary resistance to trastuzumab. Furthermore, long-term trastuzumab exposure of trastuzu- mab-resistant cell lines induces tie novo sensitivity to the EGFR-targeted agents gefltinib or cetuximab in two of three cell lines accompanied by increased EGFR expression. Together, these results indicate that primary trastuzumab resistance is not synonymous with lack of responsiveness to trastuzumab and, importantly, suggest that trastuzumab priming may sensitize trastuzumab-resistant tumors to other HER family-directed therapeutics.

Original languageEnglish (US)
Pages (from-to)2191-2194
Number of pages4
JournalCancer Research
Issue number6
StatePublished - Mar 15 2009
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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