Circulating tumor DNA as a liquid biopsy for cancer.
BACKGROUND
Targeted therapies have markedly changed the treatment of cancer over the past 10 years. However, almost all tumors acquire resistance to systemic treatment as a result of tumor heterogeneity, clonal evolution, and selection. Although genotyping is the most currently used method for categorizing tumors for clinical decisions, tumor tissues provide only a snapshot, or are often difficult to obtain. To overcome these issues, methods are needed for a rapid, cost-effective, and noninvasive identification of biomarkers at various time points during the course of disease. Because cell-free circulating tumor DNA (ctDNA) is a potential surrogate for the entire tumor genome, the use of ctDNA as a liquid biopsy may help to obtain the genetic follow-up data that are urgently needed.


BACKGROUND
This review includes recent studies exploring the diagnostic, prognostic, and predictive potential of ctDNA as a liquid biopsy in cancer. In addition, it covers biological and technical aspects, including recent advances in the analytical sensitivity and accuracy of DNA analysis as well as hurdles that have to be overcome before implementation into clinical routine.


CONCLUSIONS
Although the analysis of ctDNA is a promising area, and despite all efforts to develop suitable tools for a comprehensive analysis of tumor genomes from plasma DNA, the liquid biopsy is not yet routinely used as a clinical application. Harmonization of preanalytical and analytical procedures is needed to provide clinical standards to validate the liquid biopsy as a clinical biomarker in well-designed and sufficiently powered multicenter studies.
Institute of Human Genetics, Medical University of Graz, Graz, Austria. ellen.heitzer@medunigraz.at.
Ellen
E
Heitzer
Institute of Human Genetics, Medical University of Graz, Graz, Austria.
Peter
P
Ulz
Institute of Human Genetics, Medical University of Graz, Graz, Austria.
Jochen B
JB
Geigl
D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D001706:Biopsy; D004273:DNA, Neoplasm / Q000097:blood* / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D017422:Sequence Analysis, DNA; D018631:ras Proteins / Q000235:genetics
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins