Current Possibilities for Predicting Responses to EGFR Blockade in Metastatic Colorectal Cancer
Authors:
R. Němeček 1; M. Svoboda 1,2; O. Slabý 1,3
Authors‘ workplace:
Klinika komplexní onkologické péče LF MU a Masarykův onkologický ústav, Brno
1; Oddělení epidemiologie a genetiky nádorů, Masarykův onkologický ústav, Brno
2; CEITEC – Středoevropský technologický institut, MU, Brno
3
Published in:
Klin Onkol 2016; 29(3): 187-195
Category:
Reviews
doi:
https://doi.org/10.14735/amko2016187
Overview
Background:
The combination of modern systemic chemotherapy and anti-EGFR monoclonal antibodies improves overall survival and quality of life for patients with metastatic colorecal cancer. By contrast, the addition of anti-EGFR therapy to the treatment regime of resistant patients may lead to worse progression-free survival and overall survival. Therefore, identifying sensitive and resistant patients prior to targeted therapy of metastatic colorecal cancer is a key point during the initial decision making process. Previous research shows that primary resistance to EGFR blockade is in most cases caused by constitutive activation of signaling pathways downstream of EGFR. Of all relevant factors (mutation of KRAS, NRAS, BRAF, and PIK3CA oncogenes, inactivation of tumor suppressors PTEN and TP53, amplification of EGFR and HER2, and expression of epiregulin and amphiregulin, mikroRNA miR-31-3p, and miR-31-5p), only evaluation of KRAS and NRAS mutations has entered routine clinical practice. The role of the other markers still needs to be validated. The ongoing benefit of anti-EGFR therapy could be indicated by specific clinical parameters measured after the initiation of targeted therapy, including early tumor shrinkage, the deepness of the response, or hypomagnesemia. The accuracy of predictive diagnostic tools could be also increased by examining a combination of predictive markers using next generation sequencing methods. However, unjustified investigation of many molecular markers should be resisted as this may complicate interpretation of the results, particularly in terms of their specific clinical relevance.
Aim:
The aim of this review is to describe current possibilities with respect to predicting responses to EGFR blockade in the context of the EGFR pathway, and the utilization of such results in routine clinical practice.
Key words:
colorectal cancer – cetuximab – panitumumab – EGFR – KRAS – BRAF
The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.
Submitted:
20. 3. 2016
Accepted:
19. 4. 2016
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