Summary

Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) on cancer cells have been approved almost a decade ago for the treatment of metastatic CRC.  Shortly thereafter, evidence has been provided that the most common activating mutations in KRAS gene (exon 2 codons 12/13) were a negative predictive biomarker for EGFR-directed monoclonal antibodies. In 2009, the FDA restricted the use of both cetuximab and panitumumab to the 60% of patients without KRAS exon 2 mutations. An additional approximately 10% of patient not presenting mutations in KRAS exon 2, have been then found to harbor mutations in KRAS exons 3 or 4 or in NRAS exons 2, 3, or 4, being thus unlikely to benefit from EGFR antibodies.

 Liquid biopsy, which enables fast, non invasive blood-based biomarker test, has been recently introduced to facilitate tumor genotyping and improve patients selection for targeted therapies. DNA analysis using liquid biopsy has some clear advantages over tissue biopsy, which is inevitably affected by tumor heterogeneity, and represents one step forward in realizing the promise of precision medicine in oncology.

Companion slide kits to this video

1. Federico Rojo: Concept of Circulating Free and Tumor DNA
2. Sandra Zazo Detection of single markers in cfDNA: methodologies
3. Nerea Caravjal: Whole-genome sequencing in cfDNA: methodologies
4. Cristina Caramés: Clinical value of single mutation in ctDNA
5. Victor Moreno: Clinical value of whole-genome sequencing in cell free DNA