HER2 Signaling and Resistance to the Anti-EGFR Monoclonal Antibody Cetuximab: A Further Step toward Personalized Medicine for Patients with Colorectal Cancer
Abstract
Primary and acquired resistance to anti-epidermal growth factor receptor (EGFR) drugs are clinically relevant problems in patients with metastatic colorectal carcinoma. A complex network of molecular alterations is involved in this phenomenon. Bertotti et al. report the development of serially transplantable groups of tumor xenografts in immune-deficient mice from patient-derived, genetically characterized metastatic colorectal carcinoma samples. These experimental models (“xenopatients”) might represent a novel approach to discover and characterize the mechanisms of resistance to anti-EGFR therapy and other molecularly targeted therapies in metastatic colorectal carcinoma. In this respect, Bertotti et al. were able to identify HER2 gene amplification as one such mechanism of resistance to anti-EGFR therapy. Cancer Discovery; 1(6); 472–74. ©2011 AACR. Commentary on Bertotti et al., p. 508.
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Upregulated receptor tyrosine kinases including ERBB2, MET and IGF-1R activate the PI3K/AKT axis or reactivate the ERK pathway independently of EGFR.
“Upregulated receptor tyrosine kinases (RTKs), including ERBB2, MET and IGF-1R, activate the PI3K/AKT axis or reactivate the ERK pathway independently of EGFR [73–76].”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [73]
Amplification of ERBB2 was enriched in nonresponsive KRAS wild-type metastatic colorectal cancer.
“Importantly, amplification of ERBB2 was also enriched in nonresponsive KRAS WT mCRC [73].”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [73]
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- Authors
- Ciardiello, F., & Normanno, N.
- Affiliations
- University of Campania "Luigi Vanvitelli" (IT)
- Venue
- Cancer Discovery
- Published
- 2011-11-01
- Volume
- 1
- Issue
- 6
- Pages
- 472-474
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- OpenAlex
- W2163088994
- Cited by
- 36
- References
- 11
- Citations by year
- 2026: 2 · 2025: 2 · 2022: 2 · 2021: 6 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 2 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 2 · 2012: 1
- FWCI
- 0.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Discovery (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Keywords
- HER2 amplification, cetuximab, anti-EGFR monoclonal antibody, drug resistance, metastatic colorectal cancer, patient-derived xenografts, immunodeficient mice, targeted therapy, personalized medicine
- MeSH terms
- Cetuximab, Animals, Antibodies, Monoclonal, Female, Humans, Male, Colorectal Neoplasms, Erb-b2 Receptor Tyrosine Kinases, Receptor, ErbB-2, Xenograft Model Antitumor Assays, Antibodies, Monoclonal, Humanized
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