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HER2-targeted therapy: an emerging strategy in advanced colorectal cancer
Anna La Salvia1,2, Victoria Lopez-Gomez1, Rocio Garcia-Carbonero1,3
1a Oncology Department , Hospital Universitario 12 de Octubre , Madrid , Spain.
Introduction:
Colorectal cancer (CRC) is one of the most common malignant tumors; it is a focus of research globally, but the identification of clinically actionable oncogenic drivers remains elusive. Human epidermal growth factor receptor 2 (HER2) activation is present in approximately 5% of CRC and has acquired resistance to epidermal growth factor receptor (EGFR)-targeted therapy. Early clinical trials suggest an emerging role for personalized HER2-targeted therapy in a subset of metastatic CRC.
Areas Covered:
This manuscript reviews the relevance of HER2 activation in CRC and its potential role as a target for therapy. A literature search was conducted in June 2018 of MEDLINE and EMBASE databases for published preclinical and clinical studies; abstracts of international cancer meetings (AACR, ASCO, and ESMO) were also reviewed.
Expert Opinion:
HER2 is activated in a small but relevant proportion of CRC patients (particularly left-side, RAS wild-type, anti-EGFR resistant tumors). Dual HER2 blockade with monoclonal antibodies (mAbs) (trastuzumab and pertuzumab) or the combination of mAbs with tyrosine kinase inhibitors (trastuzumab and lapatinib) induces durable tumor responses in about one-third of HER2-positive CRC refractory to standard systemic therapy. Although immature, these results are remarkable and anticipate an expanding role for HER2 as a therapeutic target in CRC.
Insights
Human epidermal growth factor receptor 2 (HER2) activation occurs in a subset of colorectal cancers (CRC). HER2-targeted therapies show promise for patients with advanced CRC resistant to other treatments.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Colorectal cancer (CRC) is a prevalent malignancy with ongoing research into actionable oncogenic drivers.
- Human epidermal growth factor receptor 2 (HER2) activation is identified in approximately 5% of CRC cases.
- HER2 activation confers resistance to epidermal growth factor receptor (EGFR)-targeted therapies.
Purpose of the Study:
- To review the significance of HER2 activation in CRC.
- To evaluate the therapeutic potential of targeting HER2 in CRC.
Main Methods:
- Comprehensive literature search of MEDLINE and EMBASE databases up to June 2018.
- Inclusion of preclinical and clinical studies.
- Review of international cancer meeting abstracts (AACR, ASCO, ESMO).
Main Results:
- HER2 activation is found in a specific CRC subgroup (left-sided, RAS wild-type, anti-EGFR resistant).
- Dual HER2 blockade (e.g., trastuzumab, pertuzumab) or combination therapy (trastuzumab, lapatinib) yields durable responses in about one-third of HER2-positive, refractory CRC.
- Early clinical data indicate significant tumor responses.
Conclusions:
- HER2 is a relevant therapeutic target in a subset of metastatic CRC patients.
- Personalized HER2-targeted therapy is emerging as a viable treatment strategy.
- HER2 targeting demonstrates potential for expanded use in CRC treatment.
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