Recent Insights into the Development of Preclinical Trastuzumab- Resistant HER2+ Breast Cancer Models
Paula Gonzalez-Alonso1, Ion Cristobal2, Sandra Zazo1
1Group of Cancer Biomarkers, Pathology Department, Health Research Institute Fundacion Jimenez Diaz, UAM (IIS-FJD, UAM), Avda. Reyes Catolicos, E-28040 Madrid, Spain.
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.
Insights
Understanding trastuzumab resistance in HER2-amplified breast cancer is crucial. This review explores molecular mechanisms and therapeutic strategies to overcome resistance, improving outcomes for patients with HER2+ breast cancer.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- HER2 overexpression occurs in 20% of breast cancers, linked to poor prognosis.
- Trastuzumab is standard HER2-targeted therapy but faces resistance.
- Understanding resistance mechanisms is key to improving treatment efficacy.
Purpose of the Study:
- Review preclinical findings on trastuzumab resistance in HER2+ breast cancer.
- Discuss molecular mechanisms underlying acquired resistance.
- Identify potential therapeutic strategies to overcome resistance.
Main Methods:
- Comprehensive literature review of preclinical studies.
- Analysis of molecular mechanisms of trastuzumab resistance.
- Evaluation of emerging therapeutic approaches.
Main Results:
- Detailed discussion of molecular alterations driving trastuzumab resistance.
- Exploration of novel therapeutic targets and strategies.
- Identification of pathways involved in resistance.
Conclusions:
- Enhanced understanding of molecular profiles aids biomarker discovery.
- Improved diagnostic approaches and therapeutic targets for resistant breast cancer.
- Potential for novel treatments to prevent and manage trastuzumab resistance.
