Bioingeniøren (Jan 2016)
Circulating tumor DNA, a new tool for diagnosing and monitoring cancer patients?
Abstract
Background: Cell-free DNA (cfDNA) was first reported in 1948 at variable levels in blood samples, but more than two decades passed until it was discovered that it also could represent DNA from tumors. The amount cfDNA is often very low and in addition fragmented, which has made detection challenging. The revolution of methodology the last decades with regard to massive parallel sequencing (MPS) and digital PCR (dPCR) has increased the interest in detection of ctDNA. Material and methods: We have performed searches in PubMed (using the words liquid biopsy, ctDNA, cfDNA), last search was performed in May 2015. We have also included our own experiences in the field. Results/Discussion: Modern cancer treatment has an increase in new therapeutic options and treatment regimens and an increase in a more tailored approach with regard to tumor type and its molecular alterations. It is of importance to monitor the patients closer and detect therapy resistance as early as possible. Detection of molecular markers in peripheral blood can represent important tools for monitoring. Methods for detecting nucleic acids in blood, even at extreme low levels, have become available the last few years. Detection of ctDNA by the sensitive method dPCR has been limited as knowledge of which alteration to look for is needed. The development of more sensitive methods for MPS is rapid, and now very small amounts of DNA is needed to sequence many genes of interest, at a sensitivity level needed for ctDNA detection. Another challenge is a precise quantization of ctDNA. As alterations in ctDNA level are informative for therapy monitoring, protocols need standardization to make it possible to compare serial samples. The combination of increased focus on standardization of methods with more clinical trials implementing ctDNA in the protocols will eventually give more information of the clinical impact implementation of ctDNA measurements will have for cancer patients.
