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  • Title: Recent Insights into the Development of Preclinical Trastuzumab- Resistant HER2+ Breast Cancer Models.
    Author: Gonzalez-Alonso P, Cristobal I, Zazo S, Martin-Aparicio E, Chamizo C, Madoz-Gurpide J, Rovira A, Eroles P, Lluch A, Albanell J, Rojo F.
    Journal: Curr Med Chem; 2018; 25(17):1976-1998. PubMed ID: 27993109.
    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. CONCLUSION: 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.
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