Impact of efficient and inefficient therapies on CTCs and ctDNA. Impact of efficient and inefficient therapies on CTCs and ctDNA. A, if the therapy is efficient, patients are good responders, and many sensitive tumor cells in the primary tumor and/or metastases are destroyed by the treatment. As an immediate result, therapy-sensitive tumor cells (in orange) undergo apoptosis and release their tumor DNA (ctDNA) into the peripheral blood. However, the small resistant subclones of viable tumor cells (in purple) will grow and release CTCs into the blood without releasing their DNA. A small fraction of these cells may eventually undergo apoptosis and release small amounts of their DNA (purple) into the circulation. B, if the therapy is inefficient, patients are nonresponders and harbor few therapy-sensitive tumor cells (in orange) but many therapy-resistant tumor cells (in purple) before therapy. The therapy will eliminate the sensitive tumor cells, whereas the resistant cells will survive, grow, and disseminate through the bloodstream in increasing numbers without releasing high amounts of tumor DNA (in purple). Catherine Alix-Panabières, and Klaus Pantel Cancer Discov 2016;6:479-491 ©2016 by American Association for Cancer Research