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

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

Volume: 25 Issue: 17

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 and Federico Rojo*

Affiliation:

• Group of Cancer Biomarkers, Pathology Department, Health Research Institute Fundacion Jimenez Diaz, UAM (IIS-FJD, UAM), Avda. Reyes Catolicos, E-28040 Madrid,Spain

• Group of Cancer Biomarkers, Pathology Department, Health Research Institute Fundacion Jimenez Diaz, UAM (IIS-FJD, UAM), Avda. Reyes Catolicos, E-28040 Madrid,Spain

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

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.

Cite this article as:

Gonzalez-Alonso Paula*, Cristobal Ion, Zazo Sandra, Martin-Aparicio Ester, Chamizo Cristina, Madoz-Gurpide Juan, Rovira Ana, Eroles Pilar, Lluch Ana, Albanell Joan and Rojo Federico*, Recent Insights into the Development of Preclinical Trastuzumab- Resistant HER2+ Breast Cancer Models, Current Medicinal Chemistry 2018; 25 (17) . https://dx.doi.org/10.2174/0929867323666161216144659