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The emerging HER2 landscape in colorectal cancer: the key to unveil the future treatment algorithm?
Jacopo Venturini1, Giulia Massaro1, Daniele Lavacchi1
1Clinical Oncology Unit, Careggi University Hospital, Florence 50134, Italy.
Abstract:
Colorectal cancer (CRC) represents a global health threat, standing as the second leading cause of cancer-related death worldwide. Targeted therapies brought new hope for the metastatic stage, which historically bore a very poor prognosis. Human epidermal growth receptor 2 (HER2) overexpression concerns about 5 % of the metastatic CRC (mCRC) patients, including both gene amplifications and point mutations. Albeit its controversial prognostic role, preclinical and clinical data indicate HER2 as a negative predictive biomarker of response to anti-EGFR therapies. Tissue and plasma-based NGS testing, could permit a precise identification of this resistance mechanism both at baseline and during treatment, thus guiding decision-making. Furthermore, promising results come from completed and ongoing randomized trials, testing HER2 as an actionable target. In this review, we discuss the available evidence on HER2 targeting in advanced CRC, analyzing its possible future role in the treatment algorithm.
Insights
Human epidermal growth receptor 2 (HER2) is a resistance mechanism in metastatic colorectal cancer (mCRC) patients treated with anti-EGFR therapies. Targeting HER2 shows promise as an actionable strategy in advanced CRC.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Colorectal cancer (CRC) is a leading cause of cancer death globally.
- Metastatic CRC (mCRC) historically has a poor prognosis, but targeted therapies offer new hope.
- HER2 overexpression occurs in approximately 5% of mCRC patients, driven by gene amplifications or mutations.
Purpose of the Study:
- To review the evidence for HER2 targeting in advanced CRC.
- To analyze the role of HER2 as a predictive biomarker.
- To discuss the future implications of HER2-targeted therapies in the CRC treatment algorithm.
Main Methods:
- Review of preclinical and clinical data on HER2 targeting in advanced CRC.
- Analysis of next-generation sequencing (NGS) for HER2 identification.
- Evaluation of randomized trial results for HER2-targeted therapies.
Main Results:
- HER2 overexpression is associated with resistance to anti-EGFR therapies in mCRC.
- Tissue and plasma-based NGS can identify HER2 alterations for treatment guidance.
- Ongoing trials show promising results for HER2 as an actionable target.
Conclusions:
- HER2 is a significant resistance mechanism in a subset of mCRC patients.
- Precise identification of HER2 alterations via NGS is crucial for treatment decisions.
- Targeting HER2 represents a promising therapeutic strategy for advanced CRC.
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