[Prediction of EGFR blockade responses in metastatic colorectal carcinoma]. / Predikce odpovedi metastatického kolorektálního karcinomu na cílenou anti-EGFR lécbu.

ABSTRACT

The combination of modern systemic chemotherapy and anti-EGFR monoclonal antibodies improves overall survival and the quality of life for patients with metastatic colorectal cancer. By contrast, the addition of anti-EGFR therapy to the treatment regime of resistant patients may lead to worse progression-free and overall survival. Therofore, identifying sensitive and resistant patients is key during initial decision-making. A number of clinical trials show that primary resistance to EGFR blockade is in most cases caused by constitutive activation of signalling pathways downstream of EGFR. Of the many biomarkers studied, only the KRAS and NRAS mutation status has reached clinical relevance in routine practice. The other markers (BRAF and PIK3CA mutations, PTEN and TP53 inactivation, EGFR and HER-2 amplification, epiregulin and amphiregulin overexpression, microRNA miR-31-3p and miR-31-5p etc.) still need to be validated. The accuracy of predictive diagnostic tools could also be increased by a combination of predictive markers on the next generation sequencing platform.