1. Figure 1 The dynamic nature of resistance mechanisms can be
monitored in circulating tumour DNA (ctDNA)
Figure 1 | The dynamic nature of resistance mechanisms can be monitored in circulating tumour DNA (ctDNA). Digital or non-digital detection platforms can be used for the quantification of dynamic changes in the abundance of EGFR T790M mutations in ctDNA, and can be used to assess the clinical outcomes of therapy with EGFR tyrosine kinase inhibitors (TKIs). The EGFR C797S mutation causes resistance to third-generation EGFR TKIs. Next-generation ctDNA sequencing is required for the assessment of the allelic context of the C797S mutation. If the C797S is in trans with the T790M (on different EGFR alleles), tumour cells are sensitive to the combination of a first-generation and a third-generation EGFR TKI. If the C797S is in cis with the T790M, tumour cells are resistant to all EGFR TKIs either alone, or in combinations
Rosell, R. & Karachaliou, N. (2016) Using ctDNA to track EGFR and KRAS mutations in advanced-stage disease
Nat. Rev. Clin. Oncol. doi: /nrclinonc