HER2-targeted therapies beyond breast cancer - an update
Jeesun Yoon1, Do-Youn Oh2,3,4
1Division of Medical Oncology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
Abstract:
The receptor tyrosine-kinase HER2 (also known as ErbB2) is a well-established therapeutic target in patients with breast or gastric cancer selected on the basis of HER2 overexpression on immunohistochemistry and/or ERBB2 amplification on in situ hybridization. With advances in cancer molecular profiling and increased implementation of precision medicine approaches into oncology practice, actionable HER2 alterations in solid tumours have expanded to include ERBB2 mutations in addition to traditional HER2 overexpression and ERBB2 amplification. These various HER2 alterations can be found in solid tumour types beyond breast and gastric cancer, although few HER2-targeted therapeutic options have been established for the other tumour types. Nevertheless, during the 5 years since our previous Review on this topic was published in this journal, obvious and fruitful progress in the development of HER2-targeted therapies has been made, including new disease indications, innovative drugs with diverse mechanisms of action and novel frameworks for approval by regulatory authorities. These advances have culminated in the recent histology-agnostic approval of the anti-HER2 antibody-drug conjugate trastuzumab deruxtecan for patients with HER2-overexpressing solid tumours. In this new Review, we provide an update on the current development landscape of HER2-targeted therapies beyond breast cancer, as well as anticipated future HER2-directed treatment strategies to overcome resistance and thereby improve efficacy and patient outcomes.
Insights
HER2 alterations, including mutations, are increasingly recognized in various solid tumors beyond breast and gastric cancers. New HER2-targeted therapies show promise for broader applications and improved patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- HER2 (ErbB2) is a validated therapeutic target in breast and gastric cancers, identified by overexpression or amplification.
- Advances in molecular profiling reveal diverse HER2 alterations, including mutations, across various solid tumors.
- Limited HER2-targeted therapies exist for solid tumors beyond breast and gastric cancers.
Purpose of the Study:
- To review the current landscape of HER2-targeted therapies for solid tumors beyond breast and gastric cancers.
- To discuss novel HER2-directed treatment strategies and future directions.
- To highlight progress in developing new indications and regulatory approvals for HER2-targeted drugs.
Main Methods:
- Literature review of recent advancements in HER2-targeted therapy development.
- Analysis of clinical trial data and regulatory approvals for HER2-targeted agents.
- Exploration of emerging treatment strategies to overcome resistance.
Main Results:
- Significant progress in developing innovative HER2-targeted therapies with diverse mechanisms of action.
- Expansion of therapeutic options beyond traditional HER2 overexpression/amplification to include HER2 mutations.
- Recent histology-agnostic approval of trastuzumab deruxtecan for HER2-overexpressing solid tumors.
Conclusions:
- HER2-targeted therapies are evolving rapidly, offering new hope for patients with various solid tumors.
- Future strategies focus on overcoming resistance to enhance efficacy and improve patient outcomes.
- The development of novel HER2-directed treatments is expanding therapeutic possibilities in oncology.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:27Tumor Immunotherapy
02:38Mitogens and the Cell Cycle