Mechanisms of resistance to HER2 target therapy
1Oncologia Medica, Dipartimento di Medicina, Università di Verona, Policlinico Borgo Roma, Verona 37134, Italy. giampaolo.tortora@univr.it
Abstract:
In the past years, several agents targeting signaling proteins critical for breast cancer growth and dissemination entered clinical evaluation. They include drugs directed against the HER/ErbB family of receptor tyrosine kinases, especially HER2; several downstream signal transducers; and proteins involved in tumor angiogenesis and dissemination. Unfortunately, resistance to targeted agents is a quite common feature, and understanding of the molecular mechanisms predicting response or failure has become a crucial issue to optimize treatment and select patients who are the best candidates to respond. The neoadjuvant setting offers unique opportunities allowing tumor sampling and search for molecular determinants of response. A variety of tumor and host factors may account for the onset of resistance. Major progress has been made in the understanding of the mechanisms involved in the primary and acquired resistance to targeted agents, especially the anti-HER2 drugs, which play a pivotal role in the weaponry against breast cancer.
Insights
Targeted therapies for breast cancer, especially anti-HER2 drugs, show promise but resistance is common. Understanding resistance mechanisms is key to optimizing treatment and patient selection.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Targeted therapies are increasingly used for breast cancer, focusing on signaling proteins like HER2.
- Resistance to these targeted agents is a significant clinical challenge.
- Identifying mechanisms of resistance is crucial for effective treatment strategies.
Purpose of the Study:
- To review the current understanding of resistance mechanisms to targeted breast cancer therapies.
- To highlight the importance of molecular determinants in predicting treatment response.
- To emphasize the potential of the neoadjuvant setting for studying resistance.
Main Methods:
- Review of clinical evaluations of targeted agents for breast cancer.
- Analysis of molecular mechanisms underlying primary and acquired resistance.
- Focus on anti-HER2 drugs and their resistance pathways.
Main Results:
- Resistance to targeted agents is a common issue in breast cancer treatment.
- Both tumor and host factors contribute to the development of resistance.
- Significant progress has been made in understanding resistance to anti-HER2 drugs.
Conclusions:
- Understanding resistance mechanisms is vital for optimizing targeted breast cancer therapy.
- Patient selection based on molecular markers can improve treatment outcomes.
- Further research into resistance is essential for advancing breast cancer care.
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