Monitoring resistance through liquid biopsy

The clonal evolution of tumors and the development of drug resistance is arguably the most substantial hindrance in the treatment of patients with targeted therapy. In their prospective study 'Dynamic molecular analysis and clinical correlates of tumor evolution within a phase 2 trial of panitumumab-based therapy in metastatic colorectal cancer' [1], Siena et al. illustrate the value of cell-free DNA (cfDNA) in understanding the clonal evolution of colorectal cancer during anti-EGFR therapy. This study demonstrates how cfDNA may be useful in understanding mechanisms of acquired resistance to anti-EGFR therapy and how the detection of resistance mechanisms in cfDNA may correlate with clinical outcomes. In this phase II study, patients with KRAS exon 2 wild-type metastatic colorectal cancer were treated panitumumab and irinotecan. The original design of the trial was to explore the role of emergent KRAS exon 2 mutations in acquired resistance to anti-EGFR therapy. However, as the clinical importance of additional RAS family mutations became apparent, this study was expanded to explore the role of these additional RAS mutations.