title: Recent Insights into the Development of Preclinical Trastuzumab- Resistant HER2+ Breast Cancer Models.
abstract: BACKGROUND
  Overexpression and amplification of the human epidermal growth factor receptor 2 (HER2) occur in 20% of total breast carcinomas. HER2-overexpression is implicated in disease initiation and progression and associated with poor prognosis. Trastuzumab, a humanized monoclonal antibody, is the standard HER2-targeted therapy for early and metastatic HER2-amplified breast cancer patients. Trastuzumab has significantly increased clinical benefit in HER2+ metastatic and adjuvant settings; however, it is not effective for many patients due to primary or acquired resistance to the drug. During the last decade, many studies have revealed a number of novel molecular traits of HER2+ breast cancer, allowing us to uncover the molecular mechanisms involved in trastuzumab resistance and develop strategies to overcome resistance to therapy.
  
  
  OBJECTIVE
  In this review, we comprehensively addressed the current achievements in preclinical studies; we discussed molecular mechanisms of acquired trastuzumab resistance in HER2+ breast cancer models and potential therapeutic approaches based on the molecular features for HER2+ breast cancer.
  
  
  CONCLUSIONS
  Enhanced understanding of the molecular profiles in HER2+ breast cancer may lead to the identification of novel biomarkers for the development of diagnostic approaches and improvement of therapeutic targets for the prevention and treatment of trastuzumab resistant HER2+ breast cancer.
authors.affiliation: Group of Cancer Biomarkers, Pathology Department, Health Research Institute Fundacion Jimenez Diaz, UAM (IIS-FJD, UAM), Avda. Reyes Catolicos, E-28040 Madrid, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Gonzalez-Alonso
authors.affiliation: Medical Oncology Department, Oncohealth Institute, Health Research Institute Fundacion Jimenez Diaz, UAM (IIS-FJD, UAM), Avda. Reyes Catolicos, E-28040 Madrid, Spain.
authors.forename: Ion
authors.initials: I
authors.lastname: Cristobal
authors.affiliation: Group of Cancer Biomarkers, Pathology Department, Health Research Institute Fundacion Jimenez Diaz, UAM (IIS-FJD, UAM), Avda. Reyes Catolicos, E-28040 Madrid, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Zazo
authors.affiliation: Group of Cancer Biomarkers, Pathology Department, Health Research Institute Fundacion Jimenez Diaz, UAM (IIS-FJD, UAM), Avda. Reyes Catolicos, E-28040 Madrid, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Martin-Aparicio
authors.affiliation: Group of Cancer Biomarkers, Pathology Department, Health Research Institute Fundacion Jimenez Diaz, UAM (IIS-FJD, UAM), Avda. Reyes Catolicos, E-28040 Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Chamizo
authors.affiliation: Group of Cancer Biomarkers, Pathology Department, Health Research Institute Fundacion Jimenez Diaz, UAM (IIS-FJD, UAM), Avda. Reyes Catolicos, E-28040 Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Madoz-Gurpide
authors.affiliation: Cancer Research Program, Hospital del Mar Research Institute (IMIM), Medical Oncology Department, Hospital del Mar, E-08003 Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Rovira
authors.affiliation: Oncology and Hematology Department, Health Research Institute University Clinic Hospital of Valencia (INCLIVA), University of Valencia, E-46010 Valencia, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Eroles
authors.affiliation: Oncology and Hematology Department, Health Research Institute University Clinic Hospital of Valencia (INCLIVA), University of Valencia, E-46010 Valencia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.affiliation: Cancer Research Program, Hospital del Mar Research Institute (IMIM), Medical Oncology Department, Hospital del Mar, E-08003 Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Albanell
authors.affiliation: Group of Cancer Biomarkers, Pathology Department, Health Research Institute Fundacion Jimenez Diaz, UAM (IIS-FJD, UAM), Avda. Reyes Catolicos, E-28040 Madrid, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Rojo
mesh_terms: D000818:Animals; D000074322:Antineoplastic Agents, Immunological / Q000276:immunology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D000068878:Trastuzumab / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000074322:Antineoplastic Agents, Immunological; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: HER2+ breast cancer; acquired resistance; cell line; resistance model; targeted therapy; trastuzumab.