Related Experiment Video
Updated: Jul 8, 2026
Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
Potential predictive markers of response to EGFR-targeted therapies in colorectal cancer
Jean Philippe Spano1, Gérard Milano, Stéphane Vignot
1Medical Oncology Department, Pitié-Salpétrière Hospital, APHP, University of Paris 6, Paris, France. jean-philippe.spano@psl.aphp.fr
Abstract:
The importance of the epidermal growth factor receptor (EGFR) axis in tumorigenesis and tumor progression makes it an attractive target for the development of anticancer therapies. Strategies aimed at inhibiting the EGFR pathway included different classes of compounds, with monoclonal antibodies and tyrosine kinase inhibitors being the most widely-investigated agents in colorectal cancer. Although anti-EGFR therapies are active in some patients, disease will become refractory to therapy in nearly all patients. Identification of specific markers likely to predict which patients will best respond to anti-EGFR therapy is a major challenge. While the occurrence of rash is associated with greater likelihood of response, EGFR staining by immunohistochemistry at baseline is not. Among biological predictors, some studies indicate that activated EGFR, EGFR amplification, absence of KRAS mutations, PTEN expression, and low VEGFR expression are implicated in response to anti-EGFR monoclonal antibodies. Moreover, germinal gene polymorphisms, such as dinucleotide repeats polymorphism or FcgammaR polymorphism, have been shown to be associated with response to anti-EGFR therapy. Since most available data come from retrospective studies, there is a need to validate these results in prospective trials.
Insights
Predicting response to epidermal growth factor receptor (EGFR) therapies is crucial. Biomarkers like KRAS mutations and gene polymorphisms may indicate patient response to EGFR inhibitors in cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The epidermal growth factor receptor (EGFR) pathway is vital in cancer development.
- Targeting EGFR with therapies like monoclonal antibodies and tyrosine kinase inhibitors shows promise but faces resistance.
- Identifying predictive markers for anti-EGFR therapy response is a significant clinical challenge.
Purpose of the Study:
- To review and identify potential biomarkers for predicting patient response to anti-EGFR therapies.
- To highlight the need for prospective validation of identified predictive markers.
Main Methods:
- Review of existing literature on anti-EGFR therapies and predictive markers.
- Analysis of biological predictors including EGFR activation, amplification, KRAS mutations, PTEN, and VEGFR expression.
- Examination of germline gene polymorphisms (e.g., dinucleotide repeats, FcgammaR) associated with treatment response.
Main Results:
- Rash occurrence correlates with better response, but baseline EGFR immunohistochemistry does not.
- Biological markers such as activated EGFR, EGFR amplification, absence of KRAS mutations, PTEN expression, and low VEGFR expression are implicated in response.
- Germline gene polymorphisms (dinucleotide repeats, FcgammaR) are associated with anti-EGFR therapy response.
Conclusions:
- Several biological markers and gene polymorphisms show potential in predicting anti-EGFR therapy response.
- Current evidence largely stems from retrospective studies, necessitating prospective clinical trials for validation.
- Accurate prediction of response can optimize anti-EGFR therapy selection and improve patient outcomes.
Related Concept Videos
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
02:38Mitogens and the Cell Cycle
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...