CA Cancer J Clin: For the first time, the system introduces the clinical application of circulating tumor DNA and its future direction

The use of plasma circulating tumor DNA (ctDNA) for genomic analysis is developing rapidly.
of plasma ctDNA technologies in commercial and academic laboratories have been used in conventional or emerging applications.
the ongoing integration of this test to inform oncologists of treatment decisions, which is complex and challenging, but has significant potential to significantly improve patient prognostication.
The summary article entitled "Looping tumor DNA in advanced solid tumors: Clinical technology and future directions" published online by Michael L. Cheng of Harvard Medical School discusses the current role of plasma ctDNA testing in tumor therapy and outlines ongoing research that may provide reference for real-world clinical applications in the near future.
Although the current standard clinical use of plasma ctDNA testing is limited to treatment options, the ability to perform regular longitudinal analysis of patients and capture dynamic changes in ctDNA may translate into expanded clinical applications.
clinical trials are critical to establishing the clinical usefulness of plasma ctDNA analysis in addition to treatment options.
molecular manifestations of tumors in the clinical care of patients with advanced solid malignancies have enabled the rapid development of precision oncology, and the results of genomic spectrometology have guided more and more individualized treatments for cancer types.
genomic analysis traditionally uses surgically derived tumor tissue excision or biopsy specimens, focusing primarily on determining the prediction of changes in specific genes sensitive to targeted therapies.
recently, genomic spectrometry methods using plasma circulating tumor DNA (ctDNA) have been developed and have been used clinically and commercially.
have obvious advantages and disadvantages in plasma ctDNA testing, but ultimately have the potential to significantly enhance and broaden genomic spectrometry to improve cancer treatment.
this review, the current and emerging applications of plasma ctDNA testing techniques in advanced solid tumor types are discussed, and the research methods that may be translated into clinical practice in the near future are highlighted.
plasma ctDNA refers to tumor-derived DNA fragments that contain a subset of plasma cellless DNA (cfDNA), which also includes DNA from other sources in the cycle, mainly from the death of hematostocytes.
the tumor DNA is highly variable, the proportion of plasma ctDNA ranges from as low as 0.01% to the majority of plasma cfDNA.
addition, plasma ctDNA has a short half-life (estimated to be 2 hours) and plasma ctDNA levels change dynamically.
, the amount of plasma ctDNA that can be used for testing shows variability within and between patients and has an impact on the interpretation of clinical test results.
Early detection methods for plasma ctDNA spectrometry typically used polymerase chain reactions (PCRs) to identify somatic cell mutations of individual genes, such as EGFR mutations, to guide the use of EGFR tyrosine kinase inhibitors (TKIs) (NSCLCs) in advanced non-small cell lung cancer.
, however, next-generation sequencing (NGS) is most commonly used in contemporary oncology care to assess so many soytic cell changes in dozens of genes, including mutations, fusions, and copy number changes.
relatively low abundance of tumor DNA in plasma samples compared to tumor tissue, which presents a major challenge to the sensitivity of plasma-based assays.
due to insufficient plasma ctDNA content and the lack of altered genes in target NGS can lead to false negative results.
most plasma ctDNA tests are not using matching sequencing of white blood cells, and mutations in reproductive cells or somatic cell mutations in hematopoietic stem cells can lead to false positive results.
review will focus on the latest advances in the clinical use of plasma ctDNA testing by oncologists in the real world.
plasma ctDNA testing has the potential to enhance successful genomic spectrometry, especially in patients with limited tumor materials, and powerful commercial testing methods are now available for routine clinical use.
clinicians should be aware of the advantages and disadvantages of plasma ctDNA testing and tumor tissue testing, and evaluate the likelihood of false positives and false negatives when interpreting test results.
Although the current standard clinical use of plasma ctDNA testing is limited to treatment options, the ability to perform regular longitudinal analysis of patients and capture dynamic changes in ctDNA may translate into expanded clinical applications.
clinical trials are critical to establishing the clinical usefulness of plasma ctDNA analysis in addition to treatment options.