title: Clinical applications of mouse models for breast cancer engaging HER2/neu.
abstract: Human c-ErbB2 (HER2) has long been used as a marker of breast cancer (BC) for sub-categorization for the prediction of prognosis, and determination of therapeutic strategies. HER2 overexpressing BCs are more invasive/metastatic; but patients respond to monoclonal antibody therapy with trastuzumab or tyrosine kinase inhibitors, at least at early stages. To date, numerous mouse models that faithfully reproduce HER2(+) BCs have been created in mice. We recently reviewed different mouse models of BC overexpressing wild type or mutantneudriven byMMTV, neu, or doxycycline-inducible promoters. These mice have been used to demonstrate the histopathology, oncogenic signaling pathways initiated by aberrant overexpression of HER2 in the mammary epithelium, and interaction between oncogenes and tumor suppressor genes at molecular levels. In this review, we focus on their clinical applications. They can be used to test the efficacy of HER(2) inhibitors before starting clinical trials, characterize the tumor-initiating cells that could be the cause of relapse after therapy as well as to analyze the molecular mechanisms of therapeutic resistance targeting HER2.MMTV-human ErbB2 (HER2)mouse models have recently been established since the monoclonal antibody to HER2 (trastuzumab; Herceptin®) does not recognize the rat neu protein. It has been reported that early intervention with HER2 monoclonal antibody would be beneficial for preventing mammary carcinogenesis. MDA-7/IL-24 as well as naturally-occurring chemicals have also been tested usingMMTV-neumodels. Recent studies have shown thatMMTV-neumodels are useful to develop vaccines to HER2 for immunotherapy. The mouse models employing HER2/neu will be essential for future antibody or drug screenings to overcome resistance to trastuzumab or HER(2)-specific tyrosine kinase inhibitors.
authors.affiliation: The Department of Pathology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157 USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Fry
authors.affiliation: Department of Biotechnology, Sharda University, Knowledge Park III, Greater Noida 201306, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Taneja
authors.affiliation: The Department of Pathology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157 USA.
authors.forename: Kazushi
authors.initials: K
authors.lastname: Inoue
keywords: Dmp1 (Dmtf1); HER2; MDA-7/IL-24; MMTV; breast cancer; lapatinib; neu; therapy; transgenic mice; trastuzumab; vaccination