Abstract
The prognosis of metastatic colorectal cancer (mCRC) is poor. Cetuximab and panitumumab, 2 anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs), improve the overall survival of patients with RAS wild-type mCRC. However, not all patients with RAS wild-type mCRC will respond to anti-EGFR mAbs. Several retrospective trials suggest that human epidermal growth factor receptor 2 (HER2) amplification could be a predictive biomarker of resistance to anti-EGFR mAbs in patients with metastatic RAS and RAF wild-type mCRC. Dual HER2 inhibition with trastuzumab plus lapatinib or pertuzumab has shown promising preliminary anti-tumoral efficacy in RAS wild-type mCRC. Although these findings need to be confirmed in randomized trials, the data strongly support that HER2 is an actionable gene in CRC and provide the scientific rationale to test HER2 status on a routine basis in this disease. In this review, we discuss the predictive value of HER2 activation in CRC as well as its potential role as a treatment target.
Keywords:
Drug resistance; Epidermal growth factor receptor; Gene amplification; Human epidermal growth factor receptor 2; Targeted therapy.
Copyright © 2020 Elsevier Inc. All rights reserved.
MeSH terms
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Antibodies, Monoclonal, Humanized / pharmacology
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Antibodies, Monoclonal, Humanized / therapeutic use
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Biomarkers, Tumor / antagonists & inhibitors
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Biomarkers, Tumor / genetics*
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Cetuximab / pharmacology
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Cetuximab / therapeutic use
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Colorectal Neoplasms / drug therapy*
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Colorectal Neoplasms / genetics*
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Colorectal Neoplasms / pathology
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Drug Resistance, Neoplasm / genetics*
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ErbB Receptors / antagonists & inhibitors
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Gene Amplification
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Humans
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Lapatinib / pharmacology
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Lapatinib / therapeutic use
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Panitumumab / pharmacology
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Panitumumab / therapeutic use
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Predictive Value of Tests
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Prognosis
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Progression-Free Survival
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Protein Kinase Inhibitors / pharmacology
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Protein Kinase Inhibitors / therapeutic use
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Proto-Oncogene Proteins p21(ras) / genetics
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Receptor, ErbB-2 / antagonists & inhibitors
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Receptor, ErbB-2 / genetics*
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Retrospective Studies
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Trastuzumab / pharmacology
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Trastuzumab / therapeutic use
Substances
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Antibodies, Monoclonal, Humanized
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Biomarkers, Tumor
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KRAS protein, human
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Protein Kinase Inhibitors
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Lapatinib
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Panitumumab
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EGFR protein, human
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ERBB2 protein, human
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ErbB Receptors
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Receptor, ErbB-2
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Proto-Oncogene Proteins p21(ras)
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pertuzumab
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Trastuzumab
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Cetuximab