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Emerging Role of ERBB2 in Targeted Therapy for Metastatic Colorectal Cancer: Signaling Pathways to Therapeutic
Nannan Wang1, Yuepeng Cao1, Chengshuai Si1
1Department of Colorectal Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing 210009, China.
Abstract:
Despite recent improvements in the comprehensive therapy of malignancy, metastatic colorectal cancer (mCRC) continues to have a poor prognosis. Notably, 5% of mCRC cases harbor Erb-B2 receptor tyrosine kinase 2 (ERBB2) alterations. ERBB2, commonly referred to as human epidermal growth factor receptor 2, is a member of the human epidermal growth factor receptor family of protein tyrosine kinases. In addition to being a recognized therapeutic target in the treatment of gastric and breast malignancies, it is considered crucial in the management of CRC. In this review, we describe the molecular biology of ERBB2 from the perspective of biomarkers for mCRC-targeted therapy, including receptor structures, signaling pathways, gene alterations, and their detection methods. We also discuss the relationship between ERBB2 aberrations and the underlying mechanisms of resistance to anti-EGFR therapy and immunotherapy tolerance in these patients with a focus on novel targeted therapeutics and ongoing clinical trials. This may aid the development of a new standard of care in patients with ERBB2-positive mCRC.
Insights
Metastatic colorectal cancer (mCRC) with Erb-B2 receptor tyrosine kinase 2 (ERBB2) alterations has a poor prognosis. This review explores ERBB2 as a biomarker for targeted mCRC therapy, focusing on novel treatments and clinical trials.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Metastatic colorectal cancer (mCRC) presents a significant therapeutic challenge with a poor prognosis.
- A subset of mCRC cases (approximately 5%) exhibit alterations in Erb-B2 receptor tyrosine kinase 2 (ERBB2).
- ERBB2, also known as human epidermal growth factor receptor 2, is a key protein tyrosine kinase with established roles in other cancers.
Purpose of the Study:
- To review the molecular biology of ERBB2 in the context of mCRC.
- To highlight ERBB2 as a potential biomarker for targeted mCRC therapies.
- To discuss novel therapeutic strategies and ongoing clinical trials for ERBB2-positive mCRC.
Main Methods:
- Review of existing literature on ERBB2 molecular biology, signaling, and alterations in mCRC.
- Analysis of detection methods for ERBB2 gene alterations.
- Discussion of resistance mechanisms to current therapies and emerging targeted treatments.
Main Results:
- ERBB2 alterations are present in a specific fraction of mCRC patients.
- Understanding ERBB2 structure, signaling, and alterations is crucial for developing targeted therapies.
- ERBB2 aberrations are linked to resistance to anti-EGFR therapy and immunotherapy.
Conclusions:
- ERBB2 is a critical target for novel therapeutic development in mCRC.
- Targeting ERBB2 may overcome resistance mechanisms and improve outcomes in ERBB2-positive mCRC.
- Further research and clinical trials are essential to establish ERBB2-targeted therapies as a new standard of care for mCRC.
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