The spatial and temporal genomic heterogeneity of various
tumor types and advances in technology have stimulated the development of
circulating tumor DNA (ctDNA) genotyping. ctDNA was developed as a non-invasive, cost-effective alternative to
tumor biopsy when such biopsy is associated with significant risk, when
tumor tissue is insufficient or inaccessible, and/or when repeated assessment of
tumor molecular abnormalities is needed to optimize treatment. The role of ctDNA is now well established in the clinical decision in certain alterations and
tumors, such as the
epidermal growth factor receptor (EGFR) mutation in
non-small cell lung cancer and the v-Ki-ras2 kirsten rat
sarcoma viral oncogene homolog (KRAS) mutation in
colorectal cancer. The role of ctDNA analysis in other
tumor types remains to be validated. Evolving data indicate the association of ctDNA level with
tumor burden, and the usefulness of ctDNA analysis in assessing
minimal residual disease, in understanding mechanisms of resistance to treatment, and in dynamically guiding
therapy. ctDNA analysis is increasingly used to select
therapy. Carefully designed clinical trials that use ctDNA analysis will increase the rate of patients who receive targeted
therapy, will elucidate our understanding of evolution of
tumor biology and will accelerate drug development and implementation of
precision medicine. In this article we provide a critical overview of clinical trials and evolving data of ctDNA analysis in specific
tumors and across
tumor types.