Recent Insights into the Development of Preclinical Trastuzumab- Resistant HER2+ Breast Cancer Models

Author(s): Paula Gonzalez-Alonso*, Ion Cristobal, Sandra Zazo, Ester Martin-Aparicio, Cristina Chamizo, Juan Madoz-Gurpide, Ana Rovira, Pilar Eroles, Ana Lluch, Joan Albanell, Federico Rojo*.

Journal Name: Current Medicinal Chemistry

Volume 25 , Issue 17 , 2018

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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.

Keywords: HER2+ breast cancer, targeted therapy, trastuzumab, acquired resistance, cell line, resistance model.

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Article Details

VOLUME: 25
ISSUE: 17
Year: 2018
Page: [1976 - 1998]
Pages: 23
DOI: 10.2174/0929867323666161216144659
Price: $58

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