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

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

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

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
Volume69
Issue number6
DOIs
StatePublished - Mar 15 2009

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Breast Neoplasms
Epidermal Growth Factor Receptor
Cell Line
Trastuzumab
Combination Drug Therapy
Therapeutics
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Narayan, M., Wilken, J. A., Harris, L. N., Baron, A. T., Kimbler, K. D., & Maihle, N. J. (2009). Trastuzumab-lnduced HER reprogramming in "Resistant" breast carcinoma cells. Cancer Research, 69(6), 2191-2194. https://doi.org/10.1158/0008-5472.CAN-08-1056

Trastuzumab-lnduced HER reprogramming in "Resistant" breast carcinoma cells. / Narayan, Murli; Wilken, Jason A.; Harris, Lyndsay N.; Baron, Andre T.; Kimbler, Kimberly D.; Maihle, Nita Jane.

In: Cancer Research, Vol. 69, No. 6, 15.03.2009, p. 2191-2194.

Research output: Contribution to journalArticle

Narayan, M, Wilken, JA, Harris, LN, Baron, AT, Kimbler, KD & Maihle, NJ 2009, 'Trastuzumab-lnduced HER reprogramming in "Resistant" breast carcinoma cells', Cancer Research, vol. 69, no. 6, pp. 2191-2194. https://doi.org/10.1158/0008-5472.CAN-08-1056
Narayan M, Wilken JA, Harris LN, Baron AT, Kimbler KD, Maihle NJ. Trastuzumab-lnduced HER reprogramming in "Resistant" breast carcinoma cells. Cancer Research. 2009 Mar 15;69(6):2191-2194. https://doi.org/10.1158/0008-5472.CAN-08-1056
Narayan, Murli ; Wilken, Jason A. ; Harris, Lyndsay N. ; Baron, Andre T. ; Kimbler, Kimberly D. ; Maihle, Nita Jane. / Trastuzumab-lnduced HER reprogramming in "Resistant" breast carcinoma cells. In: Cancer Research. 2009 ; Vol. 69, No. 6. pp. 2191-2194.
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